In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors

Nass, Karol; Redecke, Lars; Perbandt, M.; Yefanov, O.; Klinge, M.; Koopmann, R.; Stellato, F.; Gabdulkhakov, A.; Schönherr, R.; Rehders, D.; Lahey-Rudolph, J. M.; Aquila, A.; Barty, A.; Basu, S.; Doak, R. B.; Duden, R.; Frank, M.; Fromme, R.; Kassemeyer, S.; Katona, G.; Kirian, R.; Liu, H.; Majoul, I.; Martin-Garcia, J. M.; Messerschmidt, M.; Shoeman, R. L.; Weierstall, U.; Westenhoff, S.; White, T. A.; Williams, G. J.; Yoon, C. H.; Zatsepin, N.; Fromme, P.; Duszenko, M.; Chapman, H. N.; Betzel, C.

doi:10.1038/s41467-020-14484-w

Title: In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors

Abstract

Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5’-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

Authors:

^[1]; Redecke, Lars ^[2];

^[3]; Yefanov, O. ^[4]; Klinge, M. ^[5];

^[6]; Stellato, F. ^[7]; Gabdulkhakov, A. ^[8]; Schönherr, R. ^[9]; Rehders, D. ^[10];

^[11]; Aquila, A. ^[12]; Barty, A. ^[4]; Basu, S. ^[13]; Doak, R. B. ^[14]; Duden, R. ^[15];

^[16];

^[17]; Kassemeyer, S. ^[18];

^[19] more »

Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Paul Scherrer Inst. (PSI), Villigen (Switzerland)
Inst. of Biochemistry and Molecular Biology, Hamburg (Germany). Joint Lab. for Structural Biology of Infection and Inflammation; Univ. of Hamburg (Germany); Univ. of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Lübeck (Germany); Deutsches Elektronen Synchrotron (DESY), Hamburg (Germany)
Univ. of Hamburg, at Deutsches Elektronen-Synchrotron (DESY) (Germany); The Hamburg Centre for Ultrafast Imaging (CUI), Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Inst. of Biochemistry and Molecular Biology, Hamburg (Germany). Joint Lab. for Structural Biology of Infection and Inflammation; Univ. of Hamburg (Germany); Univ. of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); BioAgilytix Europe GmbH, Hamburg (Germany)
Univ. of Tübingen (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. di Roma Tor Vergata, Rome (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Rome (Italy)
Russian Academy of Sciences, Moscow Region (Russia)
Univ. of Lübeck (Germany); Deutsches Elektronen Synchrotron (DESY), Hamburg (Germany)
Inst. of Biochemistry and Molecular Biology, Hamburg (Germany). Joint Lab. for Structural Biology of Infection and Inflammation; Univ. of Hamburg (Germany); Univ. of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); BODE Chemie GmbH, Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Lübeck (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
Arizona State Univ., Tempe, AZ (United States); European Molecular Biology Lab. (EMBL), Grenoble (France)
Arizona State Univ., Tempe, AZ (United States); Max Planck Inst. for Medical Research, Heidelberg (Germany)
Univ. of Lübeck (Germany)
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Arizona State Univ., Tempe, AZ (United States)
Max-Planck-Inst. for Medical Research, Heidelberg (Germany)
Univ. of Gothenburg (Sweden)
Arizona State Univ., Tempe, AZ (United States); Beijing Computational Science Research Center (China)
SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS); Arizona State Univ., Tempe, AZ (United States)
SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS); Brookhaven National Lab. (BNL), Upton, NY (United States)
Arizona State Univ., Tempe, AZ (United States); La Trobe Univ., VIC (Australia)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); The Hamburg Centre for Ultrafast Imaging (CUI), Hamburg (Germany); Univ. of Hamburg (Germany)

Publication Date:: 2020-01-30

Research Org.:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); German Research Foundation (DFG); Helmholtz Excellence Network; National Science Foundation (NSF); German Federal Ministry for Education and Research (BMBF); Joachim-Herz-Stiftung Hamburg; UCOP Lab Fee Program; USDOE Laboratory Directed Research and Development (LDRD) Program; Swedish Research Council (VR); Knut and Alice Wallenberg Foundation

OSTI Identifier:: 1603290

Alternate Identifier(s):: OSTI ID: 1605174

Report Number(s):: BNL-213686-2020-JAAM
Journal ID: ISSN 2041-1723

Grant/Contract Number:: SC0012704; MCB-1021557; 01KX0806; 01KX0807; 05K16GUA; 05K18FLA; AC52-07NA27344; 118036; AC02-76SF00515

Resource Type:: Accepted Manuscript

Journal Name:: Nature Communications

Additional Journal Information:: Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2041-1723

Publisher:: Nature Publishing Group

Country of Publication:: United States

Language:: English

Subject:: 36 MATERIALS SCIENCE; Biochemistry; X-ray crystallography

Citation Formats


                    Nass, Karol, Redecke, Lars, Perbandt, M., Yefanov, O., Klinge, M., Koopmann, R., Stellato, F., Gabdulkhakov, A., Schönherr, R., Rehders, D., Lahey-Rudolph, J. M., Aquila, A., Barty, A., Basu, S., Doak, R. B., Duden, R., Frank, M., Fromme, R., Kassemeyer, S., Katona, G., Kirian, R., Liu, H., Majoul, I., Martin-Garcia, J. M., Messerschmidt, M., Shoeman, R. L., Weierstall, U., Westenhoff, S., White, T. A., Williams, G. J., Yoon, C. H., Zatsepin, N., Fromme, P., Duszenko, M., Chapman, H. N., and Betzel, C. In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors.  United States: N. p., 2020. 
        Web.  doi:10.1038/s41467-020-14484-w.

Copy to clipboard


                    Nass, Karol, Redecke, Lars, Perbandt, M., Yefanov, O., Klinge, M., Koopmann, R., Stellato, F., Gabdulkhakov, A., Schönherr, R., Rehders, D., Lahey-Rudolph, J. M., Aquila, A., Barty, A., Basu, S., Doak, R. B., Duden, R., Frank, M., Fromme, R., Kassemeyer, S., Katona, G., Kirian, R., Liu, H., Majoul, I., Martin-Garcia, J. M., Messerschmidt, M., Shoeman, R. L., Weierstall, U., Westenhoff, S., White, T. A., Williams, G. J., Yoon, C. H., Zatsepin, N., Fromme, P., Duszenko, M., Chapman, H. N., & Betzel, C. In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors.  United States.  doi:https://doi.org/10.1038/s41467-020-14484-w

Copy to clipboard


                    Nass, Karol, Redecke, Lars, Perbandt, M., Yefanov, O., Klinge, M., Koopmann, R., Stellato, F., Gabdulkhakov, A., Schönherr, R., Rehders, D., Lahey-Rudolph, J. M., Aquila, A., Barty, A., Basu, S., Doak, R. B., Duden, R., Frank, M., Fromme, R., Kassemeyer, S., Katona, G., Kirian, R., Liu, H., Majoul, I., Martin-Garcia, J. M., Messerschmidt, M., Shoeman, R. L., Weierstall, U., Westenhoff, S., White, T. A., Williams, G. J., Yoon, C. H., Zatsepin, N., Fromme, P., Duszenko, M., Chapman, H. N., and Betzel, C. Thu .  
        "In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors".  United States.  doi:https://doi.org/10.1038/s41467-020-14484-w.  https://www.osti.gov/servlets/purl/1603290.

Copy to clipboard


                    
@article{osti_1603290,

  title        = {In cellulo crystallization of Trypanosoma brucei IMP dehydrogenase enables the identification of genuine co-factors},

  author       = {Nass, Karol and Redecke, Lars and Perbandt, M. and Yefanov, O. and Klinge, M. and Koopmann, R. and Stellato, F. and Gabdulkhakov, A. and Schönherr, R. and Rehders, D. and Lahey-Rudolph, J. M. and Aquila, A. and Barty, A. and Basu, S. and Doak, R. B. and Duden, R. and Frank, M. and Fromme, R. and Kassemeyer, S. and Katona, G. and Kirian, R. and Liu, H. and Majoul, I. and Martin-Garcia, J. M. and Messerschmidt, M. and Shoeman, R. L. and Weierstall, U. and Westenhoff, S. and White, T. A. and Williams, G. J. and Yoon, C. H. and Zatsepin, N. and Fromme, P. and Duszenko, M. and Chapman, H. N. and Betzel, C.},

  abstractNote = {Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5’-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.},

  doi          = {10.1038/s41467-020-14484-w},

  journal      = {Nature Communications},

  number       = 1,

  volume       = 11,

  place        = {United States},

  year         = {2020},

  month        = {1}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

DOI: https://doi.org/10.1038/s41467-020-14484-w

Other availability

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Serial femtosecond crystallography: A revolution in structural biology
journal, July 2016

Martin-Garcia, Jose M.; Conrad, Chelsie E.; Coe, Jesse
Archives of Biochemistry and Biophysics, Vol. 602
DOI: 10.1016/j.abb.2016.03.036

Serial femtosecond crystallography: the first five years
journal, February 2015

Schlichting, Ilme
IUCrJ, Vol. 2, Issue 2, p. 246-255
DOI: 10.1107/S205225251402702X

Serial crystallography at synchrotrons and X-ray lasers
journal, February 2017

Standfuss, Jörg; Spence, John
IUCrJ, Vol. 4, Issue 2
DOI: 10.1107/S2052252517001877

Femtosecond X-ray protein nanocrystallography
journal, February 2011

Chapman, Henry N.; Fromme, Petra; Barty, Anton
Nature, Vol. 470, Issue 7332, p. 73-77
DOI: 10.1038/nature09750

Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams
journal, February 2015

Nass, Karol; Foucar, Lutz; Barends, Thomas R. M.
Journal of Synchrotron Radiation, Vol. 22, Issue 2
DOI: 10.1107/S1600577515002349

Radiation damage in protein crystallography at X-ray free-electron lasers
journal, January 2019

Nass, Karol
Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 2
DOI: 10.1107/S2059798319000317

Protein crystallization in living cells
journal, June 2018

Schönherr, Robert; Rudolph, Janine Mia; Redecke, Lars
Biological Chemistry, Vol. 399, Issue 7
DOI: 10.1515/hsz-2018-0158

Protein crystallization in vivo
journal, April 2006

Doye, J.; Poon, W.
Current Opinion in Colloid & Interface Science, Vol. 11, Issue 1
DOI: 10.1016/j.cocis.2005.10.002

The molecular organization of cypovirus polyhedra
journal, March 2007

Coulibaly, Fasséli; Chiu, Elaine; Ikeda, Keiko
Nature, Vol. 446, Issue 7131
DOI: 10.1038/nature05628

In vivo protein crystallization in combination with highly brilliant radiation sources offers novel opportunities for the structural analysis of post-translationally modified eukaryotic proteins
journal, July 2015

Duszenko, Michael; Redecke, Lars; Mudogo, Celestin Nzanzu
Acta Crystallographica Section F Structural Biology Communications, Vol. 71, Issue 8
DOI: 10.1107/S2053230X15011450

Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser
journal, November 2012

Redecke, L.; Nass, K.; DePonte, D. P.
Science, Vol. 339, Issue 6116
DOI: 10.1126/science.1229663

A Diffraction-Quality Protein Crystal Processed as an Autophagic Cargo
journal, April 2015

Tsutsui, Hidekazu; Jinno, Yuka; Shoda, Keiko
Molecular Cell, Vol. 58, Issue 1
DOI: 10.1016/j.molcel.2015.02.007

An in cellulo-derived structure of PAK4 in complex with its inhibitor Inka1
journal, November 2015

Baskaran, Yohendran; Ang, Khay C.; Anekal, Praju V.
Nature Communications, Vol. 6, Issue 1
DOI: 10.1038/ncomms9681

De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure
journal, September 2016

Colletier, Jacques-Philippe; Sawaya, Michael R.; Gingery, Mari
Nature, Vol. 539, Issue 7627
DOI: 10.1038/nature19825

Kinetic Mechanism of Human Inosine 5‘-Monophosphate Dehydrogenase Type II: Random Addition of Substrates and Ordered Release of Products ^†
journal, July 1997

Wang, Wen; Hedstrom, Lizbeth
Biochemistry, Vol. 36, Issue 28
DOI: 10.1021/bi970226n

Inosine monophosphate dehydrogenase as a target for antiviral, anticancer, antimicrobial and immunosuppressive therapeutics
journal, January 2010

Braun-Sand, Sonja B.; Peetz, Matthew
Future Medicinal Chemistry, Vol. 2, Issue 1
DOI: 10.4155/fmc.09.147

Inosine 5′-monophosphate dehydrogenase inhibitors as antimicrobial agents: recent progress and future perspectives
journal, August 2015

Shah, Chetan P.; Kharkar, Prashant S.
Future Medicinal Chemistry, Vol. 7, Issue 11
DOI: 10.4155/fmc.15.72

Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening
journal, November 2018

Sarwono, Albertus Eka Yudistira; Mitsuhashi, Shinya; Kabir, Mohammad Hazzaz Bin
Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 34, Issue 1
DOI: 10.1080/14756366.2018.1540474

Sleeping Sickness in the ‘Omics Era
journal, April 2018

Tiberti, Natalia; Sanchez, Jean-Charles
PROTEOMICS - Clinical Applications, Vol. 12, Issue 4
DOI: 10.1002/prca.201700041

Characterization of the novel Trypanosoma brucei inosine 5′-monophosphate dehydrogenase
journal, February 2013

Bessho, Tomoaki; Morii, Shoko; Kusumoto, Toshihide
Parasitology, Vol. 140, Issue 6
DOI: 10.1017/S0031182012002090

Human African trypanosomiasis: pharmacological re-engagement with a neglected disease
journal, December 2007

Barrett, M. P.; Boykin, D. W.; Brun, R.
British Journal of Pharmacology, Vol. 152, Issue 8
DOI: 10.1038/sj.bjp.0707354

High-throughput decoding of antitrypanosomal drug efficacy and resistance
journal, January 2012

Alsford, Sam; Eckert, Sabine; Baker, Nicola
Nature, Vol. 482, Issue 7384
DOI: 10.1038/nature10771

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

The structure of a domain common to archaebacteria and the homocystinuria disease protein
journal, January 1997

Bateman, Alex
Trends in Biochemical Sciences, Vol. 22, Issue 1
DOI: 10.1016/S0968-0004(96)30046-7

A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases
journal, June 2017

Buey, Rubén M.; Fernández-Justel, David; Marcos-Alcalde, Íñigo
Scientific Reports, Vol. 7, Issue 1
DOI: 10.1038/s41598-017-02805-x

MgATP Regulates Allostery and Fiber Formation in IMPDHs
journal, June 2013

Labesse, Gilles; Alexandre, Thomas; Vaupré, Laurène
Structure, Vol. 21, Issue 6
DOI: 10.1016/j.str.2013.03.011

A Nucleotide-Dependent Conformational Switch Controls the Polymerization of Human IMP Dehydrogenases to Modulate their Catalytic Activity
journal, March 2019

Fernández-Justel, David; Núñez, Rafael; Martín-Benito, Jaime
Journal of Molecular Biology, Vol. 431, Issue 5
DOI: 10.1016/j.jmb.2019.01.020

In vivo protein crystallization opens new routes in structural biology
journal, January 2012

Koopmann, Rudolf; Cupelli, Karolina; Redecke, Lars
Nature Methods, Vol. 9, Issue 3
DOI: 10.1038/nmeth.1859

Real-time investigation of dynamic protein crystallization in living cells
journal, July 2015

Schönherr, R.; Klinge, M.; Rudolph, J. M.
Structural Dynamics, Vol. 2, Issue 4
DOI: 10.1063/1.4921591

Firefly luciferase is targeted to peroxisomes in mammalian cells.
journal, May 1987

Keller, G. A.; Gould, S.; Deluca, M.
Proceedings of the National Academy of Sciences, Vol. 84, Issue 10
DOI: 10.1073/pnas.84.10.3264

Protein transport into peroxisomes: Knowns and unknowns
journal, August 2017

Francisco, Tânia; Rodrigues, Tony A.; Dias, Ana F.
BioEssays, Vol. 39, Issue 10
DOI: 10.1002/bies.201700047

Cheetah : software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data
journal, May 2014

Barty, Anton; Kirian, Richard A.; Maia, Filipe R. N. C.
Journal of Applied Crystallography, Vol. 47, Issue 3
DOI: 10.1107/S1600576714007626

CrystFEL : a software suite for snapshot serial crystallography
journal, March 2012

White, Thomas A.; Kirian, Richard A.; Martin, Andrew V.
Journal of Applied Crystallography, Vol. 45, Issue 2
DOI: 10.1107/S0021889812002312

XGANDALF – extended gradient descent algorithm for lattice finding
journal, August 2019

Gevorkov, Yaroslav; Yefanov, Oleksandr; Barty, Anton
Acta Crystallographica Section A Foundations and Advances, Vol. 75, Issue 5
DOI: 10.1107/S2053273319010593

Accurate determination of segmented X-ray detector geometry
journal, January 2015

Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius
Optics Express, Vol. 23, Issue 22
DOI: 10.1364/OE.23.028459

IMP Dehydrogenase: Structure, Mechanism, and Inhibition
journal, July 2009

Hedstrom, Lizbeth
Chemical Reviews, Vol. 109, Issue 7
DOI: 10.1021/cr900021w

Characteristics and Crystal Structure of Bacterial Inosine-5‘-monophosphate Dehydrogenase ^† ^, ^‡
journal, April 1999

Zhang, Rong-guang; Evans, Gwyndaf; Rotella, Frank J.
Biochemistry, Vol. 38, Issue 15
DOI: 10.1021/bi982858v

Crystal Structure of Tritrichomonas foetus Inosine Monophosphate Dehydrogenase in Complex with the Inhibitor Ribavirin Monophosphate Reveals a Catalysis-dependent Ion-binding Site
journal, September 2002

Prosise, Glen L.; Wu, Jim Zhen; Luecke, Hartmut
Journal of Biological Chemistry, Vol. 277, Issue 52
DOI: 10.1074/jbc.M208330200

De novo GTP Biosynthesis Is Critical for Virulence of the Fungal Pathogen Cryptococcus neoformans
journal, October 2012

Morrow, Carl A.; Valkov, Eugene; Stamp, Anna
PLoS Pathogens, Vol. 8, Issue 10
DOI: 10.1371/journal.ppat.1002957

Structure of Pseudomonas aeruginosa inosine 5′-monophosphate dehydrogenase
journal, February 2013

Rao, Vincenzo A.; Shepherd, Sharon M.; Owen, Richard
Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 69, Issue 3
DOI: 10.1107/S1744309113002352

Increased riboflavin production by manipulation of inosine 5′-monophosphate dehydrogenase in Ashbya gossypii
journal, July 2015

Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Balsera, Mónica
Applied Microbiology and Biotechnology, Vol. 99, Issue 22
DOI: 10.1007/s00253-015-6710-2

Bacillus anthracis Inosine 5′-Monophosphate Dehydrogenase in Action: The First Bacterial Series of Structures of Phosphate Ion-, Substrate-, and Product-Bound Complexes
journal, July 2012

Makowska-Grzyska, Magdalena; Kim, Youngchang; Wu, Ruiying
Biochemistry, Vol. 51, Issue 31
DOI: 10.1021/bi300511w

Two Classes of Bacterial IMPDHs according to Their Quaternary Structures and Catalytic Properties
journal, February 2015

Alexandre, Thomas; Rayna, Bertrand; Munier-Lehmann, Hélène
PLOS ONE, Vol. 10, Issue 2
DOI: 10.1371/journal.pone.0116578

Crystallographic studies of two variants of Pseudomonas aeruginosa IMPDH with impaired allosteric regulation
journal, August 2015

Labesse, Gilles; Alexandre, Thomas; Gelin, Muriel
Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 9
DOI: 10.1107/S1399004715013115

First-in-class allosteric inhibitors of bacterial IMPDHs
journal, April 2019

Alexandre, Thomas; Lupan, Alexandru; Helynck, Olivier
European Journal of Medicinal Chemistry, Vol. 167
DOI: 10.1016/j.ejmech.2019.01.064

A pipeline for structure determination of in vivo -grown crystals using in cellulo diffraction
journal, March 2016

Boudes, Marion; Garriga, Damià; Fryga, Andrew
Acta Crystallographica Section D Structural Biology, Vol. 72, Issue 4
DOI: 10.1107/S2059798316002369

CBS domains: Ligand binding sites and conformational variability
journal, December 2013

Ereño-Orbea, June; Oyenarte, Iker; Martínez-Cruz, Luis Alfonso
Archives of Biochemistry and Biophysics, Vol. 540, Issue 1-2
DOI: 10.1016/j.abb.2013.10.008

Physiological concentrations of purines and pyrimidines
journal, January 1994

Traut, Thomas W.
Molecular and Cellular Biochemistry, Vol. 140, Issue 1
DOI: 10.1007/BF00928361

First lasing and operation of an ångstrom-wavelength free-electron laser
journal, August 2010

Emma, P.; Akre, R.; Arthur, J.
Nature Photonics, Vol. 4, Issue 9
DOI: 10.1038/nphoton.2010.176

Injector for scattering measurements on fully solvated biospecies
journal, March 2012

Weierstall, U.; Spence, J. C. H.; Doak, R. B.
Review of Scientific Instruments, Vol. 83, Issue 3
DOI: 10.1063/1.3693040

An anti-settling sample delivery instrument for serial femtosecond crystallography
journal, July 2012

Lomb, Lukas; Steinbrener, Jan; Bari, Sadia
Journal of Applied Crystallography, Vol. 45, Issue 4
DOI: 10.1107/S0021889812024557

High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography
journal, May 2012

Boutet, S.; Lomb, L.; Williams, G. J.
Science, Vol. 337, Issue 6092
DOI: 10.1126/science.1217737

The Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS)
journal, March 2010

Boutet, Sébastien; J. Williams, Garth
New Journal of Physics, Vol. 12, Issue 3
DOI: 10.1088/1367-2630/12/3/035024

Phaser.MRage : automated molecular replacement
journal, October 2013

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.
Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 11
DOI: 10.1107/S0907444913022750

Coot model-building tools for molecular graphics
journal, November 2004

Emsley, Paul; Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
DOI: 10.1107/S0907444904019158

Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012

Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
DOI: 10.1107/S0907444912001308

Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions
journal, November 2004

Krissinel, E.; Henrick, K.
Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
DOI: 10.1107/S0907444904026460

Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening
text, January 2018

Sarwono, Albertus Eka Yudistira; Mitsuhashi, Shinya; Kabir, Mohammad Hazzaz Bin
Taylor & Francis
DOI: 10.6084/m9.figshare.7358447.v1

Works referencing / citing this record: