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Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate.

Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT
J Mol Biol 296 155-68 (2000)
Cited: 62 times
EuropePMC logo PMID: 10656824

Abstract

Serine hydroxymethyltransferase (EC 2.1.2.1), a member of the alpha-class of pyridoxal phosphate enzymes, catalyzes the reversible interconversion of serine and glycine, changing the chemical bonding at the C(alpha)-C(beta) bond of the serine side-chain mediated by the pyridoxal phosphate cofactor. Scission of the C(alpha)-C(beta) bond of serine substrate produces a glycine product and most likely formaldehyde, which reacts without dissociation with tetrahydropteroylglutamate cofactor. Crystal structures of the human and rabbit cytosolic serine hydroxymethyltransferases (SHMT) confirmed their close similarity in tertiary and dimeric subunit structure to each other and to aspartate aminotransferase, the archetypal alpha-class pyridoxal 5'-phosphate enzyme. We describe here the structure at 2.4 A resolution of Escherichia coli serine hydroxymethyltransferase in ternary complex with glycine and 5-formyl tetrahydropteroylglutamate, refined to an R-factor value of 17.4 % and R(free) value of 19.6 %. This structure reveals the interactions of both cofactors and glycine substrate with the enzyme. Comparison with the E. coli aspartate aminotransferase structure shows the distinctions in sequence and structure which define the folate cofactor binding site in serine hydroxymethyltransferase and the differences in orientation of the amino terminal arm, the evolution of which was necessary for elaboration of the folate binding site. Comparison with the unliganded rabbit cytosolic serine hydroxymethyltransferase structure identifies changes in the conformation of the enzyme, similar to those observed in aspartate aminotransferase, that probably accompany the binding of substrate. The tetrameric quaternary structure of liganded E. coli serine hydroxymethyltransferase also differs in symmetry and relative disposition of the functional tight dimers from that of the unliganded eukaryotic enzymes. SHMT tetramers have surface charge distributions which suggest distinctions in folate binding between eukaryotic and E. coli enzymes. The structure of the E. coli ternary complex provides the basis for a thorough investigation of its mechanism through characterization and structure determination of site mutants.

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  1. Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y. Mol Cell Proteomics 8 215-225 (2009)
  2. Decreased coenzyme A levels in ridA mutant strains of Salmonella enterica result from inactivated serine hydroxymethyltransferase. Flynn JM, Christopherson MR, Downs DM. Mol Microbiol 89 751-759 (2013)
  3. Structures of Plasmodium vivax serine hydroxymethyltransferase: implications for ligand-binding specificity and functional control. Chitnumsub P, Jaruwat A, Riangrungroj P, Ittarat W, Noytanom K, Oonanant W, Vanichthanankul J, Chuankhayan P, Maenpuen S, Chen CJ, Chaiyen P, Yuthavong Y, Leartsakulpanich U. Acta Crystallogr D Biol Crystallogr 70 3177-3186 (2014)
  4. Identification and biochemical characterization of serine hydroxymethyl transferase in the hydrogenosome of Trichomonas vaginalis. Mukherjee M, Sievers SA, Brown MT, Johnson PJ. Eukaryot Cell 5 2072-2078 (2006)
  5. Chloroplastic Serine Hydroxymethyltransferase From Medicago truncatula: A Structural Characterization. Ruszkowski M, Sekula B, Ruszkowska A, Dauter Z. Front Plant Sci 9 584 (2018)
  6. Small-angle X-ray scattering of calpain-5 reveals a highly open conformation among calpains. Gakhar L, Bassuk AG, Velez G, Khan S, Yang J, Tsang SH, Mahajan VB. J Struct Biol 196 309-318 (2016)
  7. Structure-based mechanism for early PLP-mediated steps of rabbit cytosolic serine hydroxymethyltransferase reaction. Di Salvo ML, Scarsdale JN, Kazanina G, Contestabile R, Schirch V, Wright HT. Biomed Res Int 2013 458571 (2013)
  8. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities. Chitnumsub P, Ittarat W, Jaruwat A, Noytanom K, Amornwatcharapong W, Pornthanakasem W, Chaiyen P, Yuthavong Y, Leartsakulpanich U. Acta Crystallogr D Biol Crystallogr 70 1517-1527 (2014)
  9. Computational Assessment of Bacterial Protein Structures Indicates a Selection Against Aggregation. Carija A, Pinheiro F, Iglesias V, Ventura S. Cells 8 E856 (2019)
  10. Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode. Korasick DA, Kandoth PK, Tanner JJ, Mitchum MG, Beamer LJ. J Biol Chem 295 3708-3718 (2020)
  11. Kinetic mechanism and the rate-limiting step of Plasmodium vivax serine hydroxymethyltransferase. Maenpuen S, Amornwatcharapong W, Krasatong P, Sucharitakul J, Palfey BA, Yuthavong Y, Chitnumsub P, Leartsakulpanich U, Chaiyen P. J Biol Chem 290 8656-8665 (2015)
  12. Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations. Zhang ZB, Xia YL, Dong GH, Fu YX, Liu SQ. Int J Mol Sci 22 1781 (2021)
  13. Structural and functional insight into serine hydroxymethyltransferase from Helicobacter pylori. Sodolescu A, Dian C, Terradot L, Bouzhir-Sima L, Lestini R, Myllykallio H, Skouloubris S, Liebl U. PLoS One 13 e0208850 (2018)
  14. Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors. Makino Y, Oe C, Iwama K, Suzuki S, Nishiyama A, Hasegawa K, Okuda H, Hirata K, Ueno M, Kawaji K, Sasano M, Usui E, Hosaka T, Yabuki Y, Shirouzu M, Katsumi M, Murayama K, Hayashi H, Kodama EN. Commun Biol 5 619 (2022)
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  16. Bioprocess Engineering, Transcriptome, and Intermediate Metabolite Analysis of L-Serine High-Yielding Escherichia coli W3110. Wang C, Li Q, Zhou P, Chen X, Shi J, Zhao Z. Microorganisms 10 1927 (2022)
  17. research-article Biosynthesis of Strained Amino Acids Through a PLP-Dependent Enzyme via Cryptic Halogenation. Sosa MB, Leeman JT, Washington LJ, Scheller HV, Chang MCY. bioRxiv 2023.12.13.571568 (2023)
  18. Characterization of thermostable serine hydroxymethyltransferase for β-hydroxy amino acids synthesis. Ma'ruf IF, Restiawaty E, Syihab SF, Honda K, Akhmaloka. Amino Acids 55 75-88 (2023)
  19. Physical modeling and geometric shape simulation for one-dimensional flexible objects with cylindrical surface constraints. Mei Y, Du H, Jiang Q, Xiong W. Sci Rep 13 4867 (2023)


Reviews citing this publication (2)

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  2. How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state. Giardina G, Brunotti P, Fiascarelli A, Cicalini A, Costa MG, Buckle AM, di Salvo ML, Giorgi A, Marani M, Paone A, Rinaldo S, Paiardini A, Contestabile R, Cutruzzolà F. FEBS J 282 1225-1241 (2015)
  3. l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D'Aguanno S, Bossa F. Eur J Biochem 268 6508-6525 (2001)
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  5. Alanylclavam biosynthetic genes are clustered together with one group of clavulanic acid biosynthetic genes in Streptomyces clavuligerus. Zelyas NJ, Cai H, Kwong T, Jensen SE. J Bacteriol 190 7957-7965 (2008)
  6. A three-dimensional structure of Plasmodium falciparum serine hydroxymethyltransferase in complex with glycine and 5-formyl-tetrahydrofolate. Homology modeling and molecular dynamics. França TC, Pascutti PG, Ramalho TC, Figueroa-Villar JD. Biophys Chem 115 1-10 (2005)
  7. MetR-regulated Vibrio cholerae metabolism is required for virulence. Bogard RW, Davies BW, Mekalanos JJ. mBio 3 e00236-12 (2012)
  8. Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase. Pang CK, Hunter JH, Gujjar R, Podutoori R, Bowman J, Mudeppa DG, Rathod PK. Mol Biochem Parasitol 168 74-83 (2009)
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  10. The mechanism of addition of pyridoxal 5'-phosphate to Escherichia coli apo-serine hydroxymethyltransferase. Malerba F, Bellelli A, Giorgi A, Bossa F, Contestabile R. Biochem J 404 477-485 (2007)
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  12. Properties of human and rabbit cytosolic serine hydroxymethyltransferase are changed by single nucleotide polymorphic mutations. Fu TF, Hunt S, Schirch V, Safo MK, Chen BH. Arch Biochem Biophys 442 92-101 (2005)
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  14. The C-terminal domain of dimeric serine hydroxymethyltransferase plays a key role in stabilization of the quaternary structure and cooperative unfolding of protein: domain swapping studies with enzymes having high sequence identity. Bhatt AN, Khan MY, Bhakuni V. Protein Sci 13 2184-2195 (2004)
  15. Pyridoxal phosphate inhibits dynamic subunit interchange among serine hydroxymethyltransferase tetramers. Zanetti KA, Stover PJ. J Biol Chem 278 10142-10149 (2003)
  16. Structural plasticity of thermophilic serine hydroxymethyltransferases. Paiardini A, Gianese G, Bossa F, Pascarella S. Proteins 50 122-134 (2003)
  17. Overexpression and characterization of dimeric and tetrameric forms of recombinant serine hydroxymethyltransferase from Bacillus stearothermophilus. Jala VR, Prakash V, Rao NA, Savithri HS. J Biosci 27 233-242 (2002)
  18. Structural adaptation of serine hydroxymethyltransferase to low temperatures. Siglioccolo A, Bossa F, Pascarella S. Int J Biol Macromol 46 37-46 (2010)
  19. The role of Glu74 and Tyr82 in the reaction catalyzed by sheep liver cytosolic serine hydroxymethyltransferase. Rao JV, Prakash V, Rao NA, Savithri HS. Eur J Biochem 267 5967-5976 (2000)
  20. A serine hydroxymethyltransferase from marine bacterium Shewanella algae: Isolation, purification, characterization and l-serine production. Jiang W, Xia B, Liu Z. Microbiol Res 168 477-484 (2013)
  21. Distinct biochemical properties of human serine hydroxymethyltransferase compared with the Plasmodium enzyme: implications for selective inhibition. Pinthong C, Maenpuen S, Amornwatcharapong W, Yuthavong Y, Leartsakulpanich U, Chaiyen P. FEBS J 281 2570-2583 (2014)
  22. The role of evolutionarily conserved hydrophobic contacts in the quaternary structure stability of Escherichia coli serine hydroxymethyltransferase. Florio R, Chiaraluce R, Consalvi V, Paiardini A, Catacchio B, Bossa F, Contestabile R. FEBS J 276 132-143 (2009)
  23. Conformational transitions driven by pyridoxal-5'-phosphate uptake in the psychrophilic serine hydroxymethyltransferase from Psychromonas ingrahamii. Angelaccio S, Dworkowski F, Di Bello A, Milano T, Capitani G, Pascarella S. Proteins 82 2831-2841 (2014)
  24. Folate polyglutamylation eliminates dependence of activity on enzyme concentration in mitochondrial serine hydroxymethyltransferases from Arabidopsis thaliana. Wei Z, Sun K, Sandoval FJ, Cross JM, Gordon C, Kang C, Roje S. Arch Biochem Biophys 536 87-96 (2013)
  25. A flap motif in human serine hydroxymethyltransferase is important for structural stabilization, ligand binding, and control of product release. Ubonprasert S, Jaroensuk J, Pornthanakasem W, Kamonsutthipaijit N, Wongpituk P, Mee-Udorn P, Rungrotmongkol T, Ketchart O, Chitnumsub P, Leartsakulpanich U, Chaiyen P, Maenpuen S. J Biol Chem 294 10490-10502 (2019)
  26. Preparation of optically active β-hydroxy-α-amino acid by immobilized Escherichia coli cells with serine hydroxymethyl transferase activity. Zhao GH, Li H, Liu W, Zhang WG, Zhang F, Liu Q, Jiao QC. Amino Acids 40 215-220 (2011)
  27. Serine Hydroxymethyltransferase ShrA (PA2444) Controls Rugose Small-Colony Variant Formation in Pseudomonas aeruginosa. Pu M, Sheng L, Song S, Gong T, Wood TK. Front Microbiol 9 315 (2018)
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  29. Identification of amino acid residues, essential for maintaining the tetrameric structure of sheep liver cytosolic serine hydroxymethyltransferase, by targeted mutagenesis. Jala VR, Appaji Rao N, Savithri HS. Biochem J 369 469-476 (2003)
  30. Molecular cloning and biochemical characterization of Leishmania donovani serine hydroxymethyltransferase. Vatsyayan R, Roy U. Protein Expr Purif 52 433-440 (2007)
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  32. A novel serine hydroxymethyltransferase from Arthrobacter nicotianae: characterization and improving catalytic efficiency by rational design. Jiang W, Chen L, Hu N, Yuan S, Li B, Liu Z. BMC Biotechnol 14 93 (2014)
  33. Conserved water molecules in bacterial serine hydroxymethyltransferases. Milano T, Di Salvo ML, Angelaccio S, Pascarella S. Protein Eng Des Sel 28 415-426 (2015)
  34. Characterization of a serine hydroxymethyltransferase for L-serine enzymatic production from Pseudomonas plecoglossicida. Jiang W, Xia B, Huang J, Liu Z. World J Microbiol Biotechnol 29 2067-2076 (2013)
  35. Classification of ligand molecules in PDB with graph match-based structural superposition. Shionyu-Mitsuyama C, Hijikata A, Tsuji T, Shirai T. J Struct Funct Genomics 17 135-146 (2016)
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  37. 5-Formyltetrahydrofolate promotes conformational remodeling in a methylenetetrahydrofolate reductase active site and inhibits its activity. Yamada K, Mendoza J, Koutmos M. J Biol Chem 299 102855 (2023)
  38. An enzymatic activation of formaldehyde for nucleotide methylation. Bou-Nader C, Stull FW, Pecqueur L, Simon P, Guérineau V, Royant A, Fontecave M, Lombard M, Palfey BA, Hamdane D. Nat Commun 12 4542 (2021)
  39. Arg-265: a critical residue of L.donovani cytosolic SHMT in maintaining the binding of THF and catalysis. Gandhi S, Gaur N, Krishna S, Siddiqi MI, Saxena JK. Exp Parasitol 149 16-23 (2015)
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