skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity

Abstract

α-Amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) plays an important role in L-tryptophan degradation via the kynurenine pathway. ACMSD forms a homodimer and is functionally inactive as a monomer because its catalytic assembly requires an arginine residue from a neighboring subunit. However, how the oligomeric state and self-association of ACMSD are controlled in solution remains unexplored. In this study, we demonstrate that ACMSD from Pseudomonas fluorescens can self-assemble into homodimer, tetramer, and higher-order structures. Using size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS) analysis, we investigated the ACMSD tetramer structure, and fitting the SAXS data with X-ray crystal structures of the monomeric component, we could generate a pseudo-atomic structure of the tetramer. This analysis revealed a tetramer model of ACMSD as a head-on dimer of dimers. We observed that the tetramer is catalytically more active than the dimer and is in equilibrium with the monomer and dimer. Substituting a critical residue of the dimer–dimer interface, His-110, altered the tetramer dissociation profile by increasing the higher-order oligomer portion in solution without changing the X-ray crystal structure. ACMSD self-association was affected by pH, ionic strength, and other electrostatic interactions. Alignment of ACMSD sequences revealed that His-110 is highly conserved in a few bacteria that utilize nitrobenzoicmore » acid as a sole source of carbon and energy, suggesting a dedicated functional role of ACMSD's self-assembly into the tetrameric and higher-order structures. Finally, these results indicate that the dynamic oligomerization status potentially regulates ACMSD activity and that SEC-SAXS coupled with X-ray crystallography is a powerful tool for studying protein self-association.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2];  [1]; ORCiD logo [1]
  1. Univ. of Texas, San Antonio, TX (United States)
  2. SLAC National Accelerator Lab., Menlo Park, CA (United States); Stanford Univ., CA (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1560737
Grant/Contract Number:  
AC02-76SF00515; R01GM108988; CHE-1808637
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 294; Journal Issue: 30; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; NAD biosynthesis; small-angle X-ray scattering (SAXS); protein structure; protein folding; protein dynamics; decarboxylase; X-ray crystallography; metabolism; enzyme catalysis; α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD); amidohydrolase protein self-association; SEC-SAXS; solution structure; quaternary structure; amino acid degradation

Citation Formats

Yang, Yu, Davis, Ian, Matsui, Tsutomu, Rubalcava, Ivan, and Liu, Aimin. Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity. United States: N. p., 2019. Web. doi:10.1074/jbc.ra119.009035.
Yang, Yu, Davis, Ian, Matsui, Tsutomu, Rubalcava, Ivan, & Liu, Aimin. Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity. United States. doi:10.1074/jbc.ra119.009035.
Yang, Yu, Davis, Ian, Matsui, Tsutomu, Rubalcava, Ivan, and Liu, Aimin. Wed . "Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity". United States. doi:10.1074/jbc.ra119.009035. https://www.osti.gov/servlets/purl/1560737.
@article{osti_1560737,
title = {Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity},
author = {Yang, Yu and Davis, Ian and Matsui, Tsutomu and Rubalcava, Ivan and Liu, Aimin},
abstractNote = {α-Amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) plays an important role in L-tryptophan degradation via the kynurenine pathway. ACMSD forms a homodimer and is functionally inactive as a monomer because its catalytic assembly requires an arginine residue from a neighboring subunit. However, how the oligomeric state and self-association of ACMSD are controlled in solution remains unexplored. In this study, we demonstrate that ACMSD from Pseudomonas fluorescens can self-assemble into homodimer, tetramer, and higher-order structures. Using size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS) analysis, we investigated the ACMSD tetramer structure, and fitting the SAXS data with X-ray crystal structures of the monomeric component, we could generate a pseudo-atomic structure of the tetramer. This analysis revealed a tetramer model of ACMSD as a head-on dimer of dimers. We observed that the tetramer is catalytically more active than the dimer and is in equilibrium with the monomer and dimer. Substituting a critical residue of the dimer–dimer interface, His-110, altered the tetramer dissociation profile by increasing the higher-order oligomer portion in solution without changing the X-ray crystal structure. ACMSD self-association was affected by pH, ionic strength, and other electrostatic interactions. Alignment of ACMSD sequences revealed that His-110 is highly conserved in a few bacteria that utilize nitrobenzoic acid as a sole source of carbon and energy, suggesting a dedicated functional role of ACMSD's self-assembly into the tetrameric and higher-order structures. Finally, these results indicate that the dynamic oligomerization status potentially regulates ACMSD activity and that SEC-SAXS coupled with X-ray crystallography is a powerful tool for studying protein self-association.},
doi = {10.1074/jbc.ra119.009035},
journal = {Journal of Biological Chemistry},
number = 30,
volume = 294,
place = {United States},
year = {2019},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:

Works referenced in this record:

SASBDB, a repository for biological small-angle scattering data
journal, October 2014

  • Valentini, Erica; Kikhney, Alexey G.; Previtali, Gianpietro
  • Nucleic Acids Research, Vol. 43, Issue D1
  • DOI: 10.1093/nar/gku1047

Uniqueness of ab initio shape determination in small-angle scattering
journal, April 2003

  • Volkov, Vladimir V.; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 36, Issue 3, p. 860-864
  • DOI: 10.1107/S0021889803000268

Nitroaromatic Compounds, from Synthesis to Biodegradation
journal, May 2010

  • Ju, K. -S.; Parales, R. E.
  • Microbiology and Molecular Biology Reviews, Vol. 74, Issue 2
  • DOI: 10.1128/MMBR.00006-10

Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid
journal, May 1986

  • Beal, M. Flint; Kowall, Neil W.; Ellison, David W.
  • Nature, Vol. 321, Issue 6066
  • DOI: 10.1038/321168a0

Global Rigid Body Modeling of Macromolecular Complexes against Small-Angle Scattering Data
journal, August 2005


Chemotaxis of a Ralstonia sp. SJ98 toward Different Nitroaromatic Compounds and Their Degradation
journal, March 2000

  • Samanta, Sudip K.; Bhushan, Bharat; Chauhan, Ashvini
  • Biochemical and Biophysical Research Communications, Vol. 269, Issue 1
  • DOI: 10.1006/bbrc.2000.2204

DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering
journal, January 2009

  • Franke, Daniel; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 42, Issue 2, p. 342-346
  • DOI: 10.1107/S0021889809000338

Endogenous kynurenines as targets for drug discovery and development
journal, August 2002

  • Stone, Trevor W.; Darlington, L. Gail
  • Nature Reviews Drug Discovery, Vol. 1, Issue 8
  • DOI: 10.1038/nrd870

Detection of Transient Intermediates in the Metal-Dependent Nonoxidative Decarboxylation Catalyzed by α-Amino-β-Carboxymuconate-ε-Semialdehyde Decarboxylase
journal, August 2007

  • Li, Tingfeng; Ma, John K.; Hosler, Jonathan P.
  • Journal of the American Chemical Society, Vol. 129, Issue 30
  • DOI: 10.1021/ja073648l

Kynurenines in the mammalian brain: when physiology meets pathology
journal, June 2012

  • Schwarcz, Robert; Bruno, John P.; Muchowski, Paul J.
  • Nature Reviews Neuroscience, Vol. 13, Issue 7
  • DOI: 10.1038/nrn3257

CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates
journal, December 1995

  • Svergun, D.; Barberato, C.; Koch, M. H. J.
  • Journal of Applied Crystallography, Vol. 28, Issue 6
  • DOI: 10.1107/S0021889895007047

The kynurenine pathway of tryptophan degradation as a drug target
journal, February 2004


A novel degradative pathway of 2-nitrobenzoate via 3-hydroxyanthranilate in Pseudomonas fluorescens strain KU-7
journal, September 2000


Single-molecule kinetics reveals signatures of half-sites reactivity in dihydroorotate dehydrogenase A catalysis
journal, April 2006

  • Shi, J.; Dertouzos, J.; Gafni, A.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 15
  • DOI: 10.1073/pnas.0510482103

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases
journal, February 2017

  • Hershberger, Kathleen A.; Martin, Angelical S.; Hirschey, Matthew D.
  • Nature Reviews Nephrology, Vol. 13, Issue 4
  • DOI: 10.1038/nrneph.2017.5

Reassignment of the human aldehyde dehydrogenase ALDH8A1 (ALDH12) to the kynurenine pathway in tryptophan catabolism
journal, April 2018

  • Davis, Ian; Yang, Yu; Wherritt, Daniel
  • Journal of Biological Chemistry, Vol. 293, Issue 25
  • DOI: 10.1074/jbc.RA118.003320

Small-angle scattering studies of biological macromolecules in solution
journal, September 2003


Determination of protein oligomeric structure from small-angle X-ray scattering: Determination of Protein Oligomeric Structure from SAXS
journal, February 2018

  • Korasick, David A.; Tanner, John J.
  • Protein Science, Vol. 27, Issue 4
  • DOI: 10.1002/pro.3376

Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase
journal, October 2008

  • Mochalkin, Igor; Miller, J. Richard; Evdokimov, Artem
  • Protein Science, Vol. 17, Issue 10
  • DOI: 10.1110/ps.035584.108

ATSAS 2.1 – towards automated and web-supported small-angle scattering data analysis
journal, April 2007

  • Petoukhov, Maxim V.; Konarev, Peter V.; Kikhney, Alexey G.
  • Journal of Applied Crystallography, Vol. 40, Issue s1
  • DOI: 10.1107/S0021889807002853

Salt-Induced Oligomerization of Partially Folded Intermediates of Equinatoxin II
journal, July 2004

  • Ulrih, Nataša Poklar; Anderluh, Gregor; Maček, Peter
  • Biochemistry, Vol. 43, Issue 29
  • DOI: 10.1021/bi049616h

Degradation Pathways of 2- and 4-Nitrobenzoates in Cupriavidus sp. Strain ST-14 and Construction of a Recombinant Strain, ST-14::3NBA, Capable of Degrading 3-Nitrobenzoate
journal, May 2016

  • Basu, Soumik; Pal Chowdhury, Piyali; Deb, Satamita
  • Applied and Environmental Microbiology, Vol. 82, Issue 14
  • DOI: 10.1128/AEM.00739-16

α-Amino-β-carboxymuconic-ε-semialdehyde Decarboxylase (ACMSD) Is a New Member of the Amidohydrolase Superfamily
journal, May 2006

  • Li, Tingfeng; Iwaki, Hiroaki; Fu, Rong
  • Biochemistry, Vol. 45, Issue 21
  • DOI: 10.1021/bi060108c

The Pyridine Ring of NAD Is Formed by a Nonenzymatic Pericyclic Reaction
journal, January 2005

  • Colabroy, Keri L.; Begley, Tadhg P.
  • Journal of the American Chemical Society, Vol. 127, Issue 3
  • DOI: 10.1021/ja0446395

X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution
journal, August 2007

  • Putnam, Christopher D.; Hammel, Michal; Hura, Greg L.
  • Quarterly Reviews of Biophysics, Vol. 40, Issue 3
  • DOI: 10.1017/S0033583507004635

The origin of the electrostatic perturbation in acetoacetate decarboxylase
journal, May 2009

  • Ho, Meng-Chiao; Ménétret, Jean-François; Tsuruta, Hiro
  • Nature, Vol. 459, Issue 7245
  • DOI: 10.1038/nature07938

Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities
journal, May 2018


DC-SIGN Neck Domain Is a pH-sensor Controlling Oligomerization: SAXS AND HYDRODYNAMIC STUDIES OF EXTRACELLULAR DOMAIN
journal, June 2009

  • Tabarani, Georges; Thépaut, Michel; Stroebel, David
  • Journal of Biological Chemistry, Vol. 284, Issue 32
  • DOI: 10.1074/jbc.M109.021204

A Pitcher-and-Catcher Mechanism Drives Endogenous Substrate Isomerization by a Dehydrogenase in Kynurenine Metabolism
journal, November 2016


α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD + ) Biosynthesis
journal, January 2018


Liquid-chromatography-coupled SAXS for accurate sizing of aggregating proteins
journal, June 2004

  • Mathew, Elizabeth; Mirza, Ahmed; Menhart, Nick
  • Journal of Synchrotron Radiation, Vol. 11, Issue 4
  • DOI: 10.1107/S0909049504014086

Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action
journal, January 2015

  • Huo, Lu; Davis, Ian; Liu, Fange
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms6935

Bacterial pathways for degradation of nitroaromatics
journal, January 2006

  • Symons, Zoe C.; Bruce, Neil C.
  • Natural Product Reports, Vol. 23, Issue 6
  • DOI: 10.1039/b502796a

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

Determination of Domain Structure of Proteins from X-Ray Solution Scattering
journal, June 2001


pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1
journal, March 2017


WebLogo: A Sequence Logo Generator
journal, May 2004

  • Crooks, Gavin E.; Hon, Gary; Chandonia, John-Marc
  • Genome Research, Vol. 14, Issue 6, p. 1188-1190
  • DOI: 10.1101/gr.849004

How pH Modulates the Dimer-Decamer Interconversion of 2-Cys Peroxiredoxins from the Prx1 Subfamily
journal, February 2015

  • Morais, Mariana A. B.; Giuseppe, Priscila O.; Souza, Tatiana A. C. B.
  • Journal of Biological Chemistry, Vol. 290, Issue 13
  • DOI: 10.1074/jbc.M114.619205

Half-of-the-Sites Reactivity of the Castor Δ9-18:0-Acyl Carrier Protein Desaturase
journal, July 2015

  • Liu, Qin; Chai, Jin; Moche, Martin
  • Plant Physiology, Vol. 169, Issue 1
  • DOI: 10.1104/pp.15.00622

Structural and Biochemical Characterization of Aldehyde Dehydrogenase 12, the Last Enzyme of Proline Catabolism in Plants
journal, February 2019

  • Korasick, David A.; Končitíková, Radka; Kopečná, Martina
  • Journal of Molecular Biology, Vol. 431, Issue 3
  • DOI: 10.1016/j.jmb.2018.12.010

Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis
journal, May 2006

  • Strong, M.; Sawaya, M. R.; Wang, S.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 21
  • DOI: 10.1073/pnas.0602606103

De novo NAD+ synthesis enhances mitochondrial function and improves health
journal, October 2018


The dimeric dihydroorotate dehydrogenase A from Lactococcus lactis dissociates reversibly into inactive monomers
journal, November 2002

  • Ottosen, Mette Brimheim; Björnberg, Olof; Nørager, Sofie
  • Protein Science, Vol. 11, Issue 11
  • DOI: 10.1110/ps.0220302

Prostaglandin H synthase: Resolved and unresolved mechanistic issues
journal, January 2010

  • Tsai, Ah-Lim; Kulmacz, Richard J.
  • Archives of Biochemistry and Biophysics, Vol. 493, Issue 1
  • DOI: 10.1016/j.abb.2009.08.019

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

Evidence for a Dual Role of an Active Site Histidine in α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase
journal, July 2012

  • Huo, Lu; Fielding, Andrew J.; Chen, Yan
  • Biochemistry, Vol. 51, Issue 29
  • DOI: 10.1021/bi300635b

New developments in the ATSAS program package for small-angle scattering data analysis
journal, March 2012

  • Petoukhov, Maxim V.; Franke, Daniel; Shkumatov, Alexander V.
  • Journal of Applied Crystallography, Vol. 45, Issue 2
  • DOI: 10.1107/S0021889812007662

Characterization of the oligomeric states of the CK2 α2β2 holoenzyme in solution
journal, July 2017

  • Lolli, Graziano; Naressi, Denise; Sarno, Stefania
  • Biochemical Journal, Vol. 474, Issue 14
  • DOI: 10.1042/BCJ20170189

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Biological small-angle X-ray scattering facility at the Stanford Synchrotron Radiation Laboratory
journal, April 2007

  • Smolsky, Igor L.; Liu, Ping; Niebuhr, Marc
  • Journal of Applied Crystallography, Vol. 40, Issue s1
  • DOI: 10.1107/S0021889807009624

Kinetic and Spectroscopic Characterization of ACMSD from Pseudomonas fluorescens Reveals a Pentacoordinate Mononuclear Metallocofactor
journal, September 2005

  • Li, Tingfeng; Walker, Antoinette L.; Iwaki, Hiroaki
  • Journal of the American Chemical Society, Vol. 127, Issue 35
  • DOI: 10.1021/ja0532234

Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic Acid Derivatives Is Dependent on Peroxide Tone
journal, May 2016

  • Orlando, Benjamin J.; Malkowski, Michael G.
  • Journal of Biological Chemistry, Vol. 291, Issue 29
  • DOI: 10.1074/jbc.M116.725713

Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER–Golgi interface
journal, April 2017

  • Watanabe, Satoshi; Harayama, Manami; Kanemura, Shingo
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 16
  • DOI: 10.1073/pnas.1621426114

NMRPipe: A multidimensional spectral processing system based on UNIX pipes
journal, November 1995

  • Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW.
  • Journal of Biomolecular NMR, Vol. 6, Issue 3
  • DOI: 10.1007/BF00197809

ACMSD: A Novel Target for Modulating NAD+ Homeostasis
journal, April 2019


Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health
journal, July 2017


NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
journal, April 2016


Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1
journal, December 2017

  • Bergdoll, Lucie A.; Lerch, Michael T.; Patrick, John W.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 2
  • DOI: 10.1073/pnas.1715464115

Dimers to Doughnuts:  Redox-Sensitive Oligomerization of 2-Cysteine Peroxiredoxins ,
journal, April 2002

  • Wood, Zachary A.; Poole, Leslie B.; Hantgan, Roy R.
  • Biochemistry, Vol. 41, Issue 17
  • DOI: 10.1021/bi012173m

Kynurenines in the CNS: recent advances and new questions
journal, December 2012

  • Vécsei, László; Szalárdy, Levente; Fülöp, Ferenc
  • Nature Reviews Drug Discovery, Vol. 12, Issue 1
  • DOI: 10.1038/nrd3793

Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling: Substrate Positioning in Human ACMSD
journal, November 2014

  • Huo, Lu; Liu, Fange; Iwaki, Hiroaki
  • Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 1
  • DOI: 10.1002/prot.24722

What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?
journal, May 2015


Part-of-the-sites binding and reactivity in the homooligomeric enzymes – facts and artifacts
journal, March 2018

  • Wielgus-Kutrowska, Beata; Grycuk, Tomasz; Bzowska, Agnieszka
  • Archives of Biochemistry and Biophysics, Vol. 642
  • DOI: 10.1016/j.abb.2018.01.011