3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase

Michalska, Karolina; Kowiel, Marcin; Bigelow, Lance; Endres, Michael; Gilski, Miroslaw; Jaskolski, Mariusz; Joachimiak, Andrzej

doi:10.1107/S2059798320000212

Title: 3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase

Abstract

Tryptophan synthase catalyzes the last two steps of tryptophan biosynthesis in plants, fungi and bacteria. It consists of two protein chains, designated α and β, encoded by trpA and trpB genes, that function as an αββα complex. Structural and functional features of tryptophan synthase have been extensively studied, explaining the roles of individual residues in the two active sites in catalysis and allosteric regulation. TrpA serves as a model for protein-folding studies. In 1969, Jackson and Yanofsky observed that the typically monomeric TrpA forms a small population of dimers. Dimerization was postulated to take place through an exchange of structural elements of the monomeric chains, a phenomenon later termed 3D domain swapping. The structural details of the TrpA dimer have remained unknown. Here, the crystal structure of the Streptococcus pneumoniae TrpA homodimer is reported, demonstrating 3D domain swapping in a TIM-barrel fold for the first time. The N-terminal domain comprising the H0–S1–H1–S2 elements is exchanged, while the hinge region corresponds to loop L2 linking strand S2 to helix H2′. The structural elements S2 and L2 carry the catalytic residues Glu52 and Asp63. As the S2 element is part of the swapped domain, the architecture of the catalytic apparatus in themore »« less

Authors:

Michalska, Karolina;

; Bigelow, Lance; Endres, Michael;

;

; Joachimiak, Andrzej

Publication Date:: 2020-01-31

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:: USDOE; National Institutes of Health (NIH)

OSTI Identifier:: 1617954

Alternate Identifier(s):: OSTI ID: 1660745

Grant/Contract Number:: AC02-06CH11357

Resource Type:: Published Article

Journal Name:: Acta Crystallographica. Section D. Structural Biology

Additional Journal Information:: Journal Name: Acta Crystallographica. Section D. Structural Biology Journal Volume: 76 Journal Issue: 2; Journal ID: ISSN 2059-7983

Publisher:: IUCr

Country of Publication:: United Kingdom

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; tryptophan synthase; TIM barrel; 3D domain swapping; protein oligomerization; Streptococcus pneumoniae

Citation Formats


                    Michalska, Karolina, Kowiel, Marcin, Bigelow, Lance, Endres, Michael, Gilski, Miroslaw, Jaskolski, Mariusz, and Joachimiak, Andrzej. 3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase.  United Kingdom: N. p., 2020. 
Web.  doi:10.1107/S2059798320000212.

Copy to clipboard


                    Michalska, Karolina, Kowiel, Marcin, Bigelow, Lance, Endres, Michael, Gilski, Miroslaw, Jaskolski, Mariusz, & Joachimiak, Andrzej. 3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase.  United Kingdom.  https://doi.org/10.1107/S2059798320000212

Copy to clipboard


                    Michalska, Karolina, Kowiel, Marcin, Bigelow, Lance, Endres, Michael, Gilski, Miroslaw, Jaskolski, Mariusz, and Joachimiak, Andrzej. Fri .  
"3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase".  United Kingdom.  https://doi.org/10.1107/S2059798320000212.

Copy to clipboard


                    
@article{osti_1617954,

  title        = {3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase},

  author       = {Michalska, Karolina and Kowiel, Marcin and Bigelow, Lance and Endres, Michael and Gilski, Miroslaw and Jaskolski, Mariusz and Joachimiak, Andrzej},

  abstractNote = {Tryptophan synthase catalyzes the last two steps of tryptophan biosynthesis in plants, fungi and bacteria. It consists of two protein chains, designated α and β, encoded by trpA and trpB genes, that function as an αββα complex. Structural and functional features of tryptophan synthase have been extensively studied, explaining the roles of individual residues in the two active sites in catalysis and allosteric regulation. TrpA serves as a model for protein-folding studies. In 1969, Jackson and Yanofsky observed that the typically monomeric TrpA forms a small population of dimers. Dimerization was postulated to take place through an exchange of structural elements of the monomeric chains, a phenomenon later termed 3D domain swapping. The structural details of the TrpA dimer have remained unknown. Here, the crystal structure of the Streptococcus pneumoniae TrpA homodimer is reported, demonstrating 3D domain swapping in a TIM-barrel fold for the first time. The N-terminal domain comprising the H0–S1–H1–S2 elements is exchanged, while the hinge region corresponds to loop L2 linking strand S2 to helix H2′. The structural elements S2 and L2 carry the catalytic residues Glu52 and Asp63. As the S2 element is part of the swapped domain, the architecture of the catalytic apparatus in the dimer is recreated from two protein chains. The homodimer interface overlaps with the α–β interface of the tryptophan synthase αββα heterotetramer, suggesting that the 3D domain-swapped dimer cannot form a complex with the β subunit. In the crystal, the dimers assemble into a decamer comprising two pentameric rings.},

  doi          = {10.1107/S2059798320000212},

  journal      = {Acta Crystallographica. Section D. Structural Biology},

  number       = 2,

  volume       = 76,

  place        = {United Kingdom},

  year         = {2020},

  month        = {1}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Publisher's Version of Record
https://doi.org/10.1107/S2059798320000212

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 1 work

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Restoration of Enzymic Activity by Complementation in Vitro between Mutant α Subunits of Tryptophan Synthetase and between Mutant Subunits and Fragments of the α Subunit
journal, September 1969

Jackson, D. A.; Yanofsky, C.
Journal of Biological Chemistry, Vol. 244, Issue 17
DOI: 10.1016/S0021-9258(18)93660-4

Enzymatic properties of mutant Escherichia coli tryptophan synthase alpha-subunits.
journal, October 1991

Lim, W. K.; Sarkar, S. K.; Hardman, J. K.
Journal of Biological Chemistry, Vol. 266, Issue 30
DOI: 10.1016/S0021-9258(18)54910-3

Recent developments in classical density modification
journal, March 2010

Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
DOI: 10.1107/S090744490903947X

Tryptophan synthase: the workings of a channeling nanomachine
journal, June 2008

Dunn, Michael F.; Niks, Dimitri; Ngo, Huu
Trends in Biochemical Sciences, Vol. 33, Issue 6
DOI: 10.1016/j.tibs.2008.04.008

The A Protein of the Tryptophan Synthetase of Escherichia coli
journal, May 1962

Henning, U.; Helinski, Donald R.; Chao, F. C.
Journal of Biological Chemistry, Vol. 237, Issue 5
DOI: 10.1016/S0021-9258(19)83735-3

Evolutionary relationship of two ancient protein superfolds
journal, July 2014

Farías-Rico, José Arcadio; Schmidt, Steffen; Höcker, Birte
Nature Chemical Biology, Vol. 10, Issue 9
DOI: 10.1038/nchembio.1579

Overview of the CCP 4 suite and current developments
journal, March 2011

Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
DOI: 10.1107/S0907444910045749

Tryptophan synthase: a mine for enzymologists
journal, April 2009

Raboni, Samanta; Bettati, Stefano; Mozzarelli, Andrea
Cellular and Molecular Life Sciences, Vol. 66, Issue 14
DOI: 10.1007/s00018-009-0028-0

A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase
journal, July 2017

Wellington, Samantha; Nag, Partha P.; Michalska, Karolina
Nature Chemical Biology, Vol. 13, Issue 9
DOI: 10.1038/nchembio.2420

Ultrahigh resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å
journal, April 2004

Howard, E. I.; Sanishvili, R.; Cachau, R. E.
Proteins: Structure, Function, and Bioinformatics, Vol. 55, Issue 4
DOI: 10.1002/prot.20015

Three-dimensional structure of the tryptophan synthase alpha 2 beta 2 multienzyme complex from Salmonella typhimurium.
journal, November 1988

Hyde, C. C.; Ahmed, S. A.; Padlan, E. A.
Journal of Biological Chemistry, Vol. 263, Issue 33
DOI: 10.1016/S0021-9258(19)77913-7

Evolution of substrate specificity in a retained enzyme driven by gene loss
journal, March 2017

Juárez-Vázquez, Ana Lilia; Edirisinghe, Janaka N.; Verduzco-Castro, Ernesto A.
eLife, Vol. 6
DOI: 10.7554/eLife.22679

Homodimers of Mutant Tryptophan Synthase α-Subunits in Escherichia coli
journal, November 2001

Kim, Jong Won; Kim, Eun Young; Park, Hoo Hwi
Biochemical and Biophysical Research Communications, Vol. 289, Issue 2
DOI: 10.1006/bbrc.2001.6022

One Fold with Many Functions: The Evolutionary Relationships between TIM Barrel Families Based on their Sequences, Structures and Functions
journal, August 2002

Nagano, Nozomi; Orengo, Christine A.; Thornton, Janet M.
Journal of Molecular Biology, Vol. 321, Issue 5
DOI: 10.1016/S0022-2836(02)00649-6

3D domain swapping: A mechanism for oligomer assembly
journal, December 1995

Bennett, Melanie J.; Schlunegger, Michael P.; Eisenberg, David
Protein Science, Vol. 4, Issue 12
DOI: 10.1002/pro.5560041202

Allosteric effects acting over a distance of 20-25 .ANG. in the Escherichia coli tryptophan synthase bienzyme complex increase ligand affinity and cause redistribution of covalent intermediates
journal, March 1990

Houben, Karl F.; Dunn, Michael F.
Biochemistry, Vol. 29, Issue 9
DOI: 10.1021/bi00461a028

Mapping of Unit Boundaries of a Protein: Exhaustive Search for Permissive Sites for Duplication by Complementation Analysis of Random Fragment Libraries of Tryptophan Synthase α Subunit
journal, January 2004

Hiraga, Kaori; Yamagishi, Akihiko; Oshima, Tairo
Journal of Molecular Biology, Vol. 335, Issue 4
DOI: 10.1016/j.jmb.2003.11.029

High-throughput protein purification and quality assessment for crystallization
journal, September 2011

Kim, Youngchang; Babnigg, Gyorgy; Jedrzejczak, Robert
Methods, Vol. 55, Issue 1
DOI: 10.1016/j.ymeth.2011.07.010

3DSwap: curated knowledgebase of proteins involved in 3D domain swapping
journal, January 2011

Shameer, K.; Shingate, P. N.; Manjunath, S. C. P.
Database, Vol. 2011, Issue 0
DOI: 10.1093/database/bar042

The molecular pathway for the allosteric regulation of tryptophan synthase
journal, April 2003

Raboni, Samanta; Pioselli, Barbara; Bettati, Stefano
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1647, Issue 1-2
DOI: 10.1016/S1570-9639(03)00084-0

Methods used in the structure determination of bovine mitochondrial F1 ATPase
journal, January 1996

Abrahams, J. P.; Leslie, A. G. W.
Acta Crystallographica Section D Biological Crystallography, Vol. 52, Issue 1
DOI: 10.1107/S0907444995008754

In vitro mutagenesis and overexpression of the Escherichia coli trpA gene and the partial characterization of the resultant tryptophan synthase mutant alpha-subunits.
journal, December 1986

Milton, D. L.; Napier, M. L.; Myers, R. M.
Journal of Biological Chemistry, Vol. 261, Issue 35
DOI: 10.1016/S0021-9258(18)66610-4

ACHESYM : an algorithm and server for standardized placement of macromolecular models in the unit cell
journal, November 2014

Kowiel, Marcin; Jaskolski, Mariusz; Dauter, Zbigniew
Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 12
DOI: 10.1107/S1399004714024572

XDS
journal, January 2010

Kabsch, Wolfgang
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
DOI: 10.1107/S0907444909047337

Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007

Krissinel, Evgeny; Henrick, Kim
Journal of Molecular Biology, Vol. 372, Issue 3
DOI: 10.1016/j.jmb.2007.05.022

Crystal Structure of Decameric Fructose-6-Phosphate Aldolase from Escherichia coli Reveals Inter-subunit Helix Swapping as a Structural Basis for Assembly Differences in the Transaldolase Family
journal, May 2002

Thorell, Stina; Schürmann, Melanie; Sprenger, Georg A.
Journal of Molecular Biology, Vol. 319, Issue 1
DOI: 10.1016/S0022-2836(02)00258-9

Domain swapping: entangling alliances between proteins.
journal, April 1994

Bennett, M. J.; Choe, S.; Eisenberg, D.
Proceedings of the National Academy of Sciences, Vol. 91, Issue 8
DOI: 10.1073/pnas.91.8.3127

Comparison of the Tryptophan Synthetase α Subunits of Several Species of Enterobacteriaceae
journal, January 1966

Creighton, T. E.; Helinski, D. R.; Somerville, R. L.
Journal of Bacteriology, Vol. 91, Issue 5
DOI: 10.1128/JB.91.5.1819-1826.1966

On the Structural Basis of the Catalytic Mechanism and the Regulation of the Alpha Subunit of Tryptophan Synthase from Salmonella typhimurium and BX1 from Maize, Two Evolutionarily Related Enzymes
journal, September 2005

Kulik, Victor; Hartmann, Elisabeth; Weyand, Michael
Journal of Molecular Biology, Vol. 352, Issue 3
DOI: 10.1016/j.jmb.2005.07.014

3D domain swapping, protein oligomerization, and amyloid formation.
journal, December 2001

Jaskólski, M.
Acta Biochimica Polonica, Vol. 48, Issue 4
DOI: 10.18388/abp.2001_3849

Accurate bond and angle parameters for X-ray protein structure refinement
journal, July 1991

Engh, R. A.; Huber, R.
Acta Crystallographica Section A Foundations of Crystallography, Vol. 47, Issue 4
DOI: 10.1107/S0108767391001071

The Buccaneer software for automated model building. 1. Tracing protein chains
journal, August 2006

Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 9
DOI: 10.1107/S0907444906022116

The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution
journal, March 1998

Liu, Y.; Hart, P. J.; Schlunegger, M. P.
Proceedings of the National Academy of Sciences, Vol. 95, Issue 7
DOI: 10.1073/pnas.95.7.3437

Conservation of the structure and function of bacterial tryptophan synthases
journal, May 2019

Michalska, Karolina; Gale, Jennifer; Joachimiak, Grazyna
IUCrJ, Vol. 6, Issue 4
DOI: 10.1107/S2052252519005955

Fibrillogenic Oligomers of Human Cystatin C Are Formed by Propagated Domain Swapping
journal, April 2007

Wahlbom, Maria; Wang, Xin; Lindström, Veronica
Journal of Biological Chemistry, Vol. 282, Issue 25
DOI: 10.1074/jbc.M611368200

Design of proteins from smaller fragments—learning from evolution
journal, August 2014

Höcker, Birte
Current Opinion in Structural Biology, Vol. 27
DOI: 10.1016/j.sbi.2014.04.007

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
DOI: 10.1107/S0907444909042073

Automatic protein structure solution from weak X-ray data
journal, November 2013

Skubák, Pavol; Pannu, Navraj S.
Nature Communications, Vol. 4, Issue 1
DOI: 10.1038/ncomms3777

Ligation-independent cloning of PCR products (LIC-PCR)
journal, January 1990

Aslanidis, Charalampos; de Jong, Pieter J.
Nucleic Acids Research, Vol. 18, Issue 20
DOI: 10.1093/nar/18.20.6069

Features and development of Coot
journal, March 2010

Emsley, P.; Lohkamp, B.; Scott, W. G.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
DOI: 10.1107/S0907444910007493

From ancestral peptides to designed proteins
journal, February 2018

Alva, Vikram; Lupas, Andrei N.
Current Opinion in Structural Biology, Vol. 48
DOI: 10.1016/j.sbi.2017.11.006

REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011

Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
DOI: 10.1107/S0907444911001314

AdoMet radical proteins--from structure to evolution--alignment of divergent protein sequences reveals strong secondary structure element conservation
journal, July 2004

Nicolet, Y.
Nucleic Acids Research, Vol. 32, Issue 13
DOI: 10.1093/nar/gkh728

Crystal structure refinement with SHELXL
journal, January 2015

Sheldrick, George M.
Acta Crystallographica Section C Structural Chemistry, Vol. 71, Issue 1, p. 3-8
DOI: 10.1107/S2053229614024218

A Tightly Packed Hydrophobic Cluster Directs the Formation of an Off-pathway Sub-millisecond Folding Intermediate in the α Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, March 2007

Wu, Ying; Vadrevu, Ramakrishna; Kathuria, Sagar
Journal of Molecular Biology, Vol. 366, Issue 5
DOI: 10.1016/j.jmb.2006.12.005

Cleavable C-terminal His-tag vectors for structure determination
journal, March 2010

Eschenfeldt, William H.; Maltseva, Natalia; Stols, Lucy
Journal of Structural and Functional Genomics, Vol. 11, Issue 1
DOI: 10.1007/s10969-010-9082-y

On the treatment of negative intensity observations
journal, July 1978

French, S.; Wilson, K.
Acta Crystallographica Section A, Vol. 34, Issue 4
DOI: 10.1107/S0567739478001114

A combined approach to improving large-scale production of tobacco etch virus protease
journal, September 2007

Blommel, Paul G.; Fox, Brian G.
Protein Expression and Purification, Vol. 55, Issue 1, p. 53-68
DOI: 10.1016/j.pep.2007.04.013

Helix swapping between two α/β barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg2+–oxalate
journal, May 1999

Huang, Kui; Li, Zhong; Jia, Yong
Structure, Vol. 7, Issue 5
DOI: 10.1016/S0969-2126(99)80070-7

Express Primer Tool for High-Throughput Gene Cloning and Expression
journal, December 2002

Yoon, J. R.; Laible, P. D.; Gu, M.
BioTechniques, Vol. 33, Issue 6
DOI: 10.2144/02336bc03

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations
journal, November 2017

Huang, Yongqi; Gao, Meng; Su, Zhengding
The Protein Journal, Vol. 37, Issue 1
DOI: 10.1007/s10930-017-9747-5

Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues
journal, May 2001

Rousseau, F.; Schymkowitz, J. W. H.; Wilkinson, H. R.
Proceedings of the National Academy of Sciences, Vol. 98, Issue 10
DOI: 10.1073/pnas.101542098

The Biosyntheses of Tryptophan and Niacin and their Relationships
journal, August 1951

Bonner, David M.; Yanofsky, Charles
The Journal of Nutrition, Vol. 44, Issue 4
DOI: 10.1093/jn/44.4.603

The Formation and Properties of Dimers of the Tryptophan Synthetase αSubunit of Escherichia coli
journal, September 1969

Jackson, D. A.; Yanofsky, C.
Journal of Biological Chemistry, Vol. 244, Issue 17
DOI: 10.1016/S0021-9258(18)93659-8

A Cis-Prolyl Peptide Bond Isomerization Dominates the Folding of the Alpha Subunit of Trp Synthase, a TIM Barrel Protein
journal, September 2002

Wu, Ying; Matthews, C. Robert
Journal of Molecular Biology, Vol. 322, Issue 1
DOI: 10.1016/S0022-2836(02)00737-4

Specific Structure Appears at the N terminus in the Sub-millisecond Folding Intermediate of the Alpha Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, August 2005

Wu, Ying; Vadrevu, Ramakrishna; Yang, Xiaoyan
Journal of Molecular Biology, Vol. 351, Issue 3
DOI: 10.1016/j.jmb.2005.06.006

Automation of protein purification for structural genomics
journal, March 2004

Kim, Youngchang; Dementieva, Irina; Zhou, Min
Journal of Structural and Functional Genomics, Vol. 5, Issue 1/2
DOI: 10.1023/B:JSFG.0000029206.07778.fc

Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex
journal, March 2012

Dunn, Michael F.
Archives of Biochemistry and Biophysics, Vol. 519, Issue 2
DOI: 10.1016/j.abb.2012.01.016

An Obligatory Intermediate Controls the Folding of the α-Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, April 2005

Wintrode, Patrick L.; Rojsajjakul, Teerapat; Vadrevu, Ramakrishna
Journal of Molecular Biology, Vol. 347, Issue 5
DOI: 10.1016/j.jmb.2005.01.064

Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity
journal, December 2016

Buller, Andrew R.; van Roye, Paul; Murciano-Calles, Javier
Biochemistry, Vol. 55, Issue 51
DOI: 10.1021/acs.biochem.6b01127

Purification and characterization of trp aporepressor.
journal, February 1983

Joachimiak, A.; Kelley, R. L.; Gunsalus, R. P.
Proceedings of the National Academy of Sciences, Vol. 80, Issue 3
DOI: 10.1073/pnas.80.3.668

Similar Records in DOE PAGES and OSTI.GOV collections:

Conservation of the structure and function of bacterial tryptophan synthases

Journal Article Michalska, Karolina ; Gale, Jennifer ; Joachimiak, Grazyna ; ... - IUCrJ

Tryptophan biosynthesis is one of the most characterized processes in bacteria, in which the enzymes fromSalmonella typhimuriumandEscherichia coliserve as model systems. Tryptophan synthase (TrpAB) catalyzes the final two steps of tryptophan biosynthesis in plants, fungi and bacteria. This pyridoxal 5'-phosphate (PLP)-dependent enzyme consists of two protein chains, α (TrpA) and β (TrpB), functioning as a linear αββα heterotetrameric complex containing two TrpAB units. The reaction has a complicated, multistep mechanism resulting in the β-replacement of the hydroxyl group of L-serine with an indole moiety. Recent studies have shown that functional TrpAB is required for the survival of pathogenic bacteria inmore »« less
Cited by 4
https://doi.org/10.1107/S2052252519005955

Full Text Available
Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB

Journal Article Michalska, Karolina ; Wellington, Samantha ; Maltseva, Natalia ; ... - Protein Science

Intracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for L-Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB – a bifunctional enzyme catalyzing the last two steps in L-Trp synthesis. TrpA (subunit α) converts indole-3-glycerol phosphate into indole and glyceraldehyde-3-phosphate (α reaction). The former compound is subsequently used by TrpB (subunit β) to produce L-Trp in the presence of L-Ser and a pyridoxal 5'-phosphate cofactor (β reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yetmore »« less
https://doi.org/10.1002/pro.4143
Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

Journal Article Bagautdinov, Bagautdin ; Ukita, Yoko ; Miyano, Masashi ; ... - Acta Crystallographica. Section F

The crystal structure of 3-oxoacyl-(acyl-carrier protein) synthase II from T. thermophilus HB8 has been determined at 2.0 Å resolution and compared with the structures of β-keto-ACP synthases from other sources. The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. Themore »« less
https://doi.org/10.1107/S1744309108010336
The folate-binding module of Thermus thermophilus cobalamin-dependent methionine synthase displays a distinct variation of the classical TIM barrel: a TIM barrel with a `twist'

Journal Article Yamada, Kazuhiro ; Koutmos, Markos - Acta Crystallographica. Section D. Structural Biology

Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key reaction in biology that is catalyzed by a number of enzymes in many prokaryotic and eukaryotic organisms. One classic example of such an enzyme is cobalamin-dependent methionine synthase (MS). MS is a large modular protein that utilizes an S_N2-type mechanism to catalyze the chemically challenging methyl transfer from the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to form methionine. Despite over half a century of study, many questions remain about how folate-dependent methyltransferases, and MS in particular, function. Here, the structure of the folate-binding (Fol) domain of MSmore »« less
https://doi.org/10.1107/S2059798317018290
Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon

Journal Article Xia, Chuanwu ; Fu, Zhuji ; Battaile, Kevin P. ; ... - Proceedings of the National Academy of Sciences of the United States of America

Membrane-bound mitochondrial trifunctional protein (TFP) catalyzes β-oxidation of long chain fatty acyl-CoAs, employing 2-enoyl-CoA hydratase (ECH), 3-hydroxyl-CoA dehydrogenase (HAD), and 3-ketothiolase (KT) activities consecutively. Inherited deficiency of TFP is a recessive genetic disease, manifesting in hypoketotic hypoglycemia, cardiomyopathy, and sudden death. In this work we have determined the crystal structure of human TFP at 3.6-Å resolution. The biological unit of the protein is α₂β₂. The overall structure of the heterotetramer is the same as that observed by cryo-EM methods. The two β-subunits make a tightly bound homodimer at the center, and two α-subunits are bound to each side of themore »« less
Cited by 7
https://doi.org/10.1073/pnas.1816317116

Full Text Available

Similar Records

Title: 3D domain swapping in the TIM barrel of the α subunit of Streptococcus pneumoniae tryptophan synthase

Abstract

Citation Formats

Restoration of Enzymic Activity by Complementation in Vitro between Mutant α Subunits of Tryptophan Synthetase and between Mutant Subunits and Fragments of the α Subunit journal, September 1969

Enzymatic properties of mutant Escherichia coli tryptophan synthase alpha-subunits. journal, October 1991

Recent developments in classical density modification journal, March 2010

Tryptophan synthase: the workings of a channeling nanomachine journal, June 2008

The A Protein of the Tryptophan Synthetase of Escherichia coli journal, May 1962

Evolutionary relationship of two ancient protein superfolds journal, July 2014

Overview of the CCP 4 suite and current developments journal, March 2011

Tryptophan synthase: a mine for enzymologists journal, April 2009

A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase journal, July 2017

Ultrahigh resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å journal, April 2004

Three-dimensional structure of the tryptophan synthase alpha 2 beta 2 multienzyme complex from Salmonella typhimurium. journal, November 1988

Evolution of substrate specificity in a retained enzyme driven by gene loss journal, March 2017

Homodimers of Mutant Tryptophan Synthase α-Subunits in Escherichia coli journal, November 2001

One Fold with Many Functions: The Evolutionary Relationships between TIM Barrel Families Based on their Sequences, Structures and Functions journal, August 2002

3D domain swapping: A mechanism for oligomer assembly journal, December 1995

Allosteric effects acting over a distance of 20-25 .ANG. in the Escherichia coli tryptophan synthase bienzyme complex increase ligand affinity and cause redistribution of covalent intermediates journal, March 1990

Mapping of Unit Boundaries of a Protein: Exhaustive Search for Permissive Sites for Duplication by Complementation Analysis of Random Fragment Libraries of Tryptophan Synthase α Subunit journal, January 2004

High-throughput protein purification and quality assessment for crystallization journal, September 2011

3DSwap: curated knowledgebase of proteins involved in 3D domain swapping journal, January 2011

The molecular pathway for the allosteric regulation of tryptophan synthase journal, April 2003

Methods used in the structure determination of bovine mitochondrial F1 ATPase journal, January 1996

In vitro mutagenesis and overexpression of the Escherichia coli trpA gene and the partial characterization of the resultant tryptophan synthase mutant alpha-subunits. journal, December 1986

ACHESYM : an algorithm and server for standardized placement of macromolecular models in the unit cell journal, November 2014

XDS journal, January 2010

Inference of Macromolecular Assemblies from Crystalline State journal, September 2007

Crystal Structure of Decameric Fructose-6-Phosphate Aldolase from Escherichia coli Reveals Inter-subunit Helix Swapping as a Structural Basis for Assembly Differences in the Transaldolase Family journal, May 2002

Domain swapping: entangling alliances between proteins. journal, April 1994

Comparison of the Tryptophan Synthetase α Subunits of Several Species of Enterobacteriaceae journal, January 1966

On the Structural Basis of the Catalytic Mechanism and the Regulation of the Alpha Subunit of Tryptophan Synthase from Salmonella typhimurium and BX1 from Maize, Two Evolutionarily Related Enzymes journal, September 2005

3D domain swapping, protein oligomerization, and amyloid formation. journal, December 2001

Accurate bond and angle parameters for X-ray protein structure refinement journal, July 1991

The Buccaneer software for automated model building. 1. Tracing protein chains journal, August 2006

The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution journal, March 1998

Conservation of the structure and function of bacterial tryptophan synthases journal, May 2019

Fibrillogenic Oligomers of Human Cystatin C Are Formed by Propagated Domain Swapping journal, April 2007

Design of proteins from smaller fragments—learning from evolution journal, August 2014

MolProbity : all-atom structure validation for macromolecular crystallography journal, December 2009

Automatic protein structure solution from weak X-ray data journal, November 2013

Ligation-independent cloning of PCR products (LIC-PCR) journal, January 1990

Features and development of Coot journal, March 2010

From ancestral peptides to designed proteins journal, February 2018

REFMAC 5 for the refinement of macromolecular crystal structures journal, March 2011

AdoMet radical proteins--from structure to evolution--alignment of divergent protein sequences reveals strong secondary structure element conservation journal, July 2004

Crystal structure refinement with SHELXL journal, January 2015

A Tightly Packed Hydrophobic Cluster Directs the Formation of an Off-pathway Sub-millisecond Folding Intermediate in the α Subunit of Tryptophan Synthase, a TIM Barrel Protein journal, March 2007

Cleavable C-terminal His-tag vectors for structure determination journal, March 2010

On the treatment of negative intensity observations journal, July 1978

A combined approach to improving large-scale production of tobacco etch virus protease journal, September 2007

Helix swapping between two α/β barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg2+–oxalate journal, May 1999

Express Primer Tool for High-Throughput Gene Cloning and Expression journal, December 2002

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations journal, November 2017

Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues journal, May 2001

The Biosyntheses of Tryptophan and Niacin and their Relationships journal, August 1951

The Formation and Properties of Dimers of the Tryptophan Synthetase αSubunit of Escherichia coli journal, September 1969

A Cis-Prolyl Peptide Bond Isomerization Dominates the Folding of the Alpha Subunit of Trp Synthase, a TIM Barrel Protein journal, September 2002

Specific Structure Appears at the N terminus in the Sub-millisecond Folding Intermediate of the Alpha Subunit of Tryptophan Synthase, a TIM Barrel Protein journal, August 2005

Automation of protein purification for structural genomics journal, March 2004

Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex journal, March 2012

An Obligatory Intermediate Controls the Folding of the α-Subunit of Tryptophan Synthase, a TIM Barrel Protein journal, April 2005

Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity journal, December 2016

Purification and characterization of trp aporepressor. journal, February 1983

Restoration of Enzymic Activity by Complementation in Vitro between Mutant α Subunits of Tryptophan Synthetase and between Mutant Subunits and Fragments of the α Subunit
journal, September 1969

Enzymatic properties of mutant Escherichia coli tryptophan synthase alpha-subunits.
journal, October 1991

Recent developments in classical density modification
journal, March 2010

Tryptophan synthase: the workings of a channeling nanomachine
journal, June 2008

The A Protein of the Tryptophan Synthetase of Escherichia coli
journal, May 1962

Evolutionary relationship of two ancient protein superfolds
journal, July 2014

Overview of the CCP 4 suite and current developments
journal, March 2011

Tryptophan synthase: a mine for enzymologists
journal, April 2009

A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase
journal, July 2017

Ultrahigh resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å
journal, April 2004

Three-dimensional structure of the tryptophan synthase alpha 2 beta 2 multienzyme complex from Salmonella typhimurium.
journal, November 1988

Evolution of substrate specificity in a retained enzyme driven by gene loss
journal, March 2017

Homodimers of Mutant Tryptophan Synthase α-Subunits in Escherichia coli
journal, November 2001

One Fold with Many Functions: The Evolutionary Relationships between TIM Barrel Families Based on their Sequences, Structures and Functions
journal, August 2002

3D domain swapping: A mechanism for oligomer assembly
journal, December 1995

Allosteric effects acting over a distance of 20-25 .ANG. in the Escherichia coli tryptophan synthase bienzyme complex increase ligand affinity and cause redistribution of covalent intermediates
journal, March 1990

Mapping of Unit Boundaries of a Protein: Exhaustive Search for Permissive Sites for Duplication by Complementation Analysis of Random Fragment Libraries of Tryptophan Synthase α Subunit
journal, January 2004

High-throughput protein purification and quality assessment for crystallization
journal, September 2011

3DSwap: curated knowledgebase of proteins involved in 3D domain swapping
journal, January 2011

The molecular pathway for the allosteric regulation of tryptophan synthase
journal, April 2003

Methods used in the structure determination of bovine mitochondrial F1 ATPase
journal, January 1996

In vitro mutagenesis and overexpression of the Escherichia coli trpA gene and the partial characterization of the resultant tryptophan synthase mutant alpha-subunits.
journal, December 1986

ACHESYM : an algorithm and server for standardized placement of macromolecular models in the unit cell
journal, November 2014

XDS
journal, January 2010

Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007

Crystal Structure of Decameric Fructose-6-Phosphate Aldolase from Escherichia coli Reveals Inter-subunit Helix Swapping as a Structural Basis for Assembly Differences in the Transaldolase Family
journal, May 2002

Domain swapping: entangling alliances between proteins.
journal, April 1994

Comparison of the Tryptophan Synthetase α Subunits of Several Species of Enterobacteriaceae
journal, January 1966

On the Structural Basis of the Catalytic Mechanism and the Regulation of the Alpha Subunit of Tryptophan Synthase from Salmonella typhimurium and BX1 from Maize, Two Evolutionarily Related Enzymes
journal, September 2005

3D domain swapping, protein oligomerization, and amyloid formation.
journal, December 2001

Accurate bond and angle parameters for X-ray protein structure refinement
journal, July 1991

The Buccaneer software for automated model building. 1. Tracing protein chains
journal, August 2006

The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution
journal, March 1998

Conservation of the structure and function of bacterial tryptophan synthases
journal, May 2019

Fibrillogenic Oligomers of Human Cystatin C Are Formed by Propagated Domain Swapping
journal, April 2007

Design of proteins from smaller fragments—learning from evolution
journal, August 2014

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

Automatic protein structure solution from weak X-ray data
journal, November 2013

Ligation-independent cloning of PCR products (LIC-PCR)
journal, January 1990

Features and development of Coot
journal, March 2010

From ancestral peptides to designed proteins
journal, February 2018

REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011

AdoMet radical proteins--from structure to evolution--alignment of divergent protein sequences reveals strong secondary structure element conservation
journal, July 2004

Crystal structure refinement with SHELXL
journal, January 2015

A Tightly Packed Hydrophobic Cluster Directs the Formation of an Off-pathway Sub-millisecond Folding Intermediate in the α Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, March 2007

Cleavable C-terminal His-tag vectors for structure determination
journal, March 2010

On the treatment of negative intensity observations
journal, July 1978

A combined approach to improving large-scale production of tobacco etch virus protease
journal, September 2007

Helix swapping between two α/β barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg2+–oxalate
journal, May 1999

Express Primer Tool for High-Throughput Gene Cloning and Expression
journal, December 2002

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations
journal, November 2017

Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues
journal, May 2001

The Biosyntheses of Tryptophan and Niacin and their Relationships
journal, August 1951

The Formation and Properties of Dimers of the Tryptophan Synthetase αSubunit of Escherichia coli
journal, September 1969

A Cis-Prolyl Peptide Bond Isomerization Dominates the Folding of the Alpha Subunit of Trp Synthase, a TIM Barrel Protein
journal, September 2002

Specific Structure Appears at the N terminus in the Sub-millisecond Folding Intermediate of the Alpha Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, August 2005

Automation of protein purification for structural genomics
journal, March 2004

Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex
journal, March 2012

An Obligatory Intermediate Controls the Folding of the α-Subunit of Tryptophan Synthase, a TIM Barrel Protein
journal, April 2005

Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity
journal, December 2016

Purification and characterization of trp aporepressor.
journal, February 1983