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Structure of serine acetyltransferase in complexes with CoA and its cysteine feedback inhibitor.

Olsen LR, Huang B, Vetting MW, Roderick SL
Biochemistry 43 6013-9 (2004)
Related entries: 1ssm, 1ssq

Cited: 45 times
EuropePMC logo PMID: 15147185

Abstract

Serine acetyltransferase (SAT, EC 2.3.1.30) catalyzes the CoA-dependent acetylation of the side chain hydroxyl group of l-serine to form O-acetylserine, as the first step of a two-step biosynthetic pathway in bacteria and plants leading to the formation of l-cysteine. This reaction represents a key metabolic point of regulation for the cysteine biosynthetic pathway due to its feedback inhibition by cysteine. We have determined the X-ray crystal structure of Haemophilus influenzae SAT in complexes with CoA and its cysteine feedback inhibitor. The enzyme is a 175 kDa hexamer displaying the characteristic left-handed parallel beta-helix (LbetaH) structural domain of the hexapeptide acyltransferase superfamily of enzymes. Cysteine is bound in a crevice between adjacent LbetaH domains and underneath a loop excluded from the coiled LbetaH. The proximity of its thiol group to the thiol group of CoA derived from superimposed models of the cysteine and CoA complexes confirms that cysteine is bound at the active site. Analysis of the contacts of SAT with cysteine and CoA and the conformational differences that distinguish these complexes provides a structural basis for cysteine feedback inhibition, which invokes competition between cysteine and serine binding and a cysteine-induced conformational change of the C-terminal segment of the enzyme that excludes binding of the cofactor.

Reviews - 1sst mentioned but not cited (1)

  1. New insights into the structure and function of an emerging drug target CysE. Verma D, Gupta V. 3 Biotech 11 373 (2021)

Articles - 1sst mentioned but not cited (2)

  1. Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature. Salsi E, Bayden AS, Spyrakis F, Amadasi A, Campanini B, Bettati S, Dodatko T, Cozzini P, Kellogg GE, Cook PF, Roderick SL, Mozzarelli A. J Med Chem 53 345-356 (2010)
  2. A two-step process controls the formation of the bienzyme cysteine synthase complex. Salsi E, Campanini B, Bettati S, Raboni S, Roderick SL, Cook PF, Mozzarelli A. J Biol Chem 285 12813-12822 (2010)


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  1. Selenium uptake, translocation, assimilation and metabolic fate in plants. Sors TG, Ellis DR, Salt DE. Photosynth Res 86 373-389 (2005)
  2. Functional analysis of the cysteine synthase protein complex from plants: structural, biochemical and regulatory properties. Wirtz M, Hell R. J Plant Physiol 163 273-286 (2006)
  3. Synthesis of the sulfur amino acids: cysteine and methionine. Wirtz M, Droux M. Photosynth Res 86 345-362 (2005)
  4. The cysteine regulatory complex from plants and microbes: what was old is new again. Jez JM, Dey S. Curr Opin Struct Biol 23 302-310 (2013)
  5. The serine acetyltransferase reaction: acetyl transfer from an acylpantothenyl donor to an alcohol. Johnson CM, Roderick SL, Cook PF. Arch Biochem Biophys 433 85-95 (2005)
  6. Moonlighting O-acetylserine sulfhydrylase: New functions for an old protein. Campanini B, Benoni R, Bettati S, Beck CM, Hayes CS, Mozzarelli A. Biochim Biophys Acta 1854 1184-1193 (2015)
  7. The lac operon galactoside acetyltransferase. Roderick SL. C R Biol 328 568-575 (2005)
  8. Cysteine biosynthesis in Neisseria species. Hicks JL, Mullholland CV. Microbiology (Reading) 164 1471-1480 (2018)
  9. Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses. Watanabe M, Chiba Y, Hirai MY. Front Plant Sci 12 643403 (2021)
  10. Combatting antimicrobial resistance via the cysteine biosynthesis pathway in bacterial pathogens. Hicks JL, Oldham KEA, McGarvie J, Walker EJ. Biosci Rep 42 BSR20220368 (2022)
  11. Insight into de-regulation of amino acid feedback inhibition: a focus on structure analysis method. Naz S, Liu P, Farooq U, Ma H. Microb Cell Fact 22 161 (2023)
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Articles citing this publication (30)

  1. Analysis of sulfur and selenium assimilation in Astragalus plants with varying capacities to accumulate selenium. Sors TG, Ellis DR, Na GN, Lahner B, Lee S, Leustek T, Pickering IJ, Salt DE. Plant J 42 785-797 (2005)
  2. Structural basis for interaction of O-acetylserine sulfhydrylase and serine acetyltransferase in the Arabidopsis cysteine synthase complex. Francois JA, Kumaran S, Jez JM. Plant Cell 18 3647-3655 (2006)
  3. Sulfur amino acid metabolism and its control in Lactococcus lactis IL1403. Sperandio B, Polard P, Ehrlich DS, Renault P, Guédon E. J Bacteriol 187 3762-3778 (2005)
  4. An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein. Müller A, Thomas GH, Horler R, Brannigan JA, Blagova E, Levdikov VM, Fogg MJ, Wilson KS, Wilkinson AJ. Mol Microbiol 57 143-155 (2005)
  5. Interaction of serine acetyltransferase with O-acetylserine sulfhydrylase active site: evidence from fluorescence spectroscopy. Campanini B, Speroni F, Salsi E, Cook PF, Roderick SL, Huang B, Bettati S, Mozzarelli A. Protein Sci 14 2115-2124 (2005)
  6. Structure and function of the hetero-oligomeric cysteine synthase complex in plants. Wirtz M, Birke H, Heeg C, Müller C, Hosp F, Throm C, König S, Feldman-Salit A, Rippe K, Petersen G, Wade RC, Rybin V, Scheffzek K, Hell R. J Biol Chem 285 32810-32817 (2010)
  7. The active site of O-acetylserine sulfhydrylase is the anchor point for bienzyme complex formation with serine acetyltransferase. Huang B, Vetting MW, Roderick SL. J Bacteriol 187 3201-3205 (2005)
  8. Assembly of the cysteine synthase complex and the regulatory role of protein-protein interactions. Kumaran S, Yi H, Krishnan HB, Jez JM. J Biol Chem 284 10268-10275 (2009)
  9. Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana. Hell R, Wirtz M. Arabidopsis Book 9 e0154 (2011)
  10. A mechanistic model of the cysteine synthase complex. Feldman-Salit A, Wirtz M, Hell R, Wade RC. J Mol Biol 386 37-59 (2009)
  11. On the interaction site of serine acetyltransferase in the cysteine synthase complex from Escherichia coli. Zhao C, Moriga Y, Feng B, Kumada Y, Imanaka H, Imamura K, Nakanishi K. Biochem Biophys Res Commun 341 911-916 (2006)
  12. Structural and biochemical studies of serine acetyltransferase reveal why the parasite Entamoeba histolytica cannot form a cysteine synthase complex. Kumar S, Raj I, Nagpal I, Subbarao N, Gourinath S. J Biol Chem 286 12533-12541 (2011)
  13. Fine tuning of the active site modulates specificity in the interaction of O-acetylserine sulfhydrylase isozymes with serine acetyltransferase. Spyrakis F, Felici P, Bayden AS, Salsi E, Miggiano R, Kellogg GE, Cozzini P, Cook PF, Mozzarelli A, Campanini B. Biochim Biophys Acta 1834 169-181 (2013)
  14. Sulfite reduction in mycobacteria. Pinto R, Harrison JS, Hsu T, Jacobs WR, Leyh TS. J Bacteriol 189 6714-6722 (2007)
  15. Isoform-dependent feedback regulation of serine O-acetyltransferase isoenzymes involved in L-cysteine biosynthesis of Entamoeba histolytica. Hussain S, Ali V, Jeelani G, Nozaki T. Mol Biochem Parasitol 163 39-47 (2009)
  16. Left handed beta helix models for mammalian prion fibrils. Kunes KC, Clark SC, Cox DL, Singh RR. Prion 2 81-90 (2008)
  17. Three-stage assembly of the cysteine synthase complex from Escherichia coli. Wang T, Leyh TS. J Biol Chem 287 4360-4367 (2012)
  18. Structure of soybean serine acetyltransferase and formation of the cysteine regulatory complex as a molecular chaperone. Yi H, Dey S, Kumaran S, Lee SG, Krishnan HB, Jez JM. J Biol Chem 288 36463-36472 (2013)
  19. Insights on the regulation of the phenylacetate degradation pathway from Escherichia coli. Fernández C, Díaz E, García JL. Environ Microbiol Rep 6 239-250 (2014)
  20. Modulation of Escherichia coli serine acetyltransferase catalytic activity in the cysteine synthase complex. Benoni R, De Bei O, Paredi G, Hayes CS, Franko N, Mozzarelli A, Bettati S, Campanini B. FEBS Lett 591 1212-1224 (2017)
  21. Structural changes and differentially expressed genes in Pseudomonas aeruginosa exposed to meropenem-ciprofloxacin combination. Siqueira VL, Cardoso RF, Caleffi-Ferracioli KR, Scodro RB, Fernandez MA, Fiorini A, Ueda-Nakamura T, Dias-Filho BP, Nakamura CV. Antimicrob Agents Chemother 58 3957-3967 (2014)
  22. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants. Tavares S, Wirtz M, Beier MP, Bogs J, Hell R, Amâncio S. Front Plant Sci 6 74 (2015)
  23. Crystal structure of serine acetyl transferase from Brucella abortus and its complex with coenzyme A. Kumar S, Kumar N, Alam N, Gourinath S. Biochim Biophys Acta 1844 1741-1748 (2014)
  24. Roles of histidines 154 and 189 and aspartate 139 in the active site of serine acetyltransferase from Haemophilus influenzae. Guan R, Roderick SL, Huang B, Cook PF. Biochemistry 47 6322-6328 (2008)
  25. Activation of an anti-bacterial toxin by the biosynthetic enzyme CysK: mechanism of binding, interaction specificity and competition with cysteine synthase. Benoni R, Beck CM, Garza-Sánchez F, Bettati S, Mozzarelli A, Hayes CS, Campanini B. Sci Rep 7 8817 (2017)
  26. Combination of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action. Rosa B, Marchetti M, Paredi G, Amenitsch H, Franko N, Benoni R, Giabbai B, De Marino MG, Mozzarelli A, Ronda L, Storici P, Campanini B, Bettati S. Int J Mol Sci 20 E5219 (2019)
  27. Structural and biochemical analyses of Microcystis aeruginosa O-acetylserine sulfhydrylases reveal a negative feedback regulation of cysteine biosynthesis. Lu M, Xu BY, Zhou K, Cheng W, Jiang YL, Chen Y, Zhou CZ. Biochim Biophys Acta 1844 308-315 (2014)
  28. Revealing the Dynamic Allosteric Changes Required for Formation of the Cysteine Synthase Complex by Hydrogen-Deuterium Exchange MS. Rosa B, Dickinson ER, Marchetti M, Campanini B, Pioselli B, Bettati S, Rand KD. Mol Cell Proteomics 20 100098 (2021)
  29. Serine acetyltransferase from Neisseria gonorrhoeae; structural and biochemical basis of inhibition. Oldham KEA, Prentice EJ, Summers EL, Hicks JL. Biochem J 479 57-74 (2022)
  30. Direct targeting of Arabidopsis cysteine synthase complexes with synthetic polypeptides to selectively deregulate cysteine synthesis. Wawrzyńska A, Kurzyk A, Mierzwińska M, Płochocka D, Wieczorek G, Sirko A. Plant Sci 207 148-157 (2013)


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