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Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe.

Goto M, Yamauchi T, Kamiya N, Miyahara I, Yoshimura T, Mihara H, Kurihara T, Hirotsu K, Esaki N
J Biol Chem 284 25944-52 (2009)
Cited: 43 times
EuropePMC logo PMID: 19640845

Abstract

D-serine is an endogenous coagonist for the N-methyl-D-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5'-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of L-serine to yield D-serine and vice versa. The enzyme also catalyzes the dehydration of D- and L-serine. Both reactions are enhanced by Mg.ATP in vivo. We have determined the structures of the following three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe: the wild-type enzyme, the wild-type enzyme in the complex with an ATP analog, and the modified enzyme in the complex with serine at 1.7, 1.9, and 2.2 A resolution, respectively. On binding of the substrate, the small domain rotates toward the large domain to close the active site. The ATP binding site was identified at the domain and the subunit interface. Computer graphics models of the wild-type enzyme complexed with L-serine and D-serine provided an insight into the catalytic mechanisms of both reactions. Lys-57 and Ser-82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique "lysino-D-alanyl" residue at the active site, also exhibits catalytic activities. The crystal-soaking experiment showed that the substrate serine was actually trapped in the active site of the modified enzyme, suggesting that the lysino-D-alanyl residue acts as a catalytic base in the same manner as inherent Lys-57 of the wild-type enzyme.

Reviews - 2zr8 mentioned but not cited (2)

  1. The Energy Landscape of Human Serine Racemase. Raboni S, Marchetti M, Faggiano S, Campanini B, Bruno S, Marchesani F, Margiotta M, Mozzarelli A. Front Mol Biosci 5 112 (2018)
  2. Human Serine Racemase: Key Residues/Active Site Motifs and Their Relation to Enzyme Function. Graham DL, Beio ML, Nelson DL, Berkowitz DB. Front Mol Biosci 6 8 (2019)

Articles - 2zr8 mentioned but not cited (3)

  1. Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe. Goto M, Yamauchi T, Kamiya N, Miyahara I, Yoshimura T, Mihara H, Kurihara T, Hirotsu K, Esaki N. J Biol Chem 284 25944-25952 (2009)
  2. Crystal structure of a zinc-dependent D-serine dehydratase from chicken kidney. Tanaka H, Senda M, Venugopalan N, Yamamoto A, Senda T, Ishida T, Horiike K. J Biol Chem 286 27548-27558 (2011)
  3. Tyrosine 121 moves revealing a ligandable pocket that couples catalysis to ATP-binding in serine racemase. Koulouris CR, Gardiner SE, Harris TK, Elvers KT, Mark Roe S, Gillespie JA, Ward SE, Grubisha O, Nicholls RA, Atack JR, Bax BD. Commun Biol 5 346 (2022)


Reviews citing this publication (6)

  1. The NMDA Receptor and Schizophrenia: From Pathophysiology to Treatment. Balu DT. Adv Pharmacol 76 351-382 (2016)
  2. Controlling reaction specificity in pyridoxal phosphate enzymes. Toney MD. Biochim Biophys Acta 1814 1407-1418 (2011)
  3. Current Advances on Structure-Function Relationships of Pyridoxal 5'-Phosphate-Dependent Enzymes. Liang J, Han Q, Tan Y, Ding H, Li J. Front Mol Biosci 6 4 (2019)
  4. Serine racemase: an unconventional enzyme for an unconventional transmitter. Wolosker H, Mori H. Amino Acids 43 1895-1904 (2012)
  5. Serine racemase: a key player in apoptosis and necrosis. Canu N, Ciotti MT, Pollegioni L. Front Synaptic Neurosci 6 9 (2014)
  6. Exploiting racemases. Femmer C, Bechtold M, Roberts TM, Panke S. Appl Microbiol Biotechnol 100 7423-7436 (2016)

Articles citing this publication (32)

  1. The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding. Smith MA, Mack V, Ebneth A, Moraes I, Felicetti B, Wood M, Schonfeld D, Mather O, Cesura A, Barker J. J Biol Chem 285 12873-12881 (2010)
  2. Conserved pyridoxal protein that regulates Ile and Val metabolism. Ito T, Iimori J, Takayama S, Moriyama A, Yamauchi A, Hemmi H, Yoshimura T. J Bacteriol 195 5439-5449 (2013)
  3. Serine racemase is involved in d-aspartate biosynthesis. Ito T, Hayashida M, Kobayashi S, Muto N, Hayashi A, Yoshimura T, Mori H. J Biochem 160 345-353 (2016)
  4. Glycolytic flux controls D-serine synthesis through glyceraldehyde-3-phosphate dehydrogenase in astrocytes. Suzuki M, Sasabe J, Miyoshi Y, Kuwasako K, Muto Y, Hamase K, Matsuoka M, Imanishi N, Aiso S. Proc Natl Acad Sci U S A 112 E2217-24 (2015)
  5. ATP binding to human serine racemase is cooperative and modulated by glycine. Marchetti M, Bruno S, Campanini B, Peracchi A, Mai N, Mozzarelli A. FEBS J 280 5853-5863 (2013)
  6. Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation of O-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR. Annunziato G, Pieroni M, Benoni R, Campanini B, Pertinhez TA, Pecchini C, Bruno A, Magalhães J, Bettati S, Franko N, Mozzarelli A, Costantino G. J Enzyme Inhib Med Chem 31 78-87 (2016)
  7. Distribution and evolution of the serine/aspartate racemase family in invertebrates. Uda K, Abe K, Dehara Y, Mizobata K, Sogawa N, Akagi Y, Saigan M, Radkov AD, Moe LA. Amino Acids 48 387-402 (2016)
  8. Regulation of human serine racemase activity and dynamics by halides, ATP and malonate. Marchetti M, Bruno S, Campanini B, Bettati S, Peracchi A, Mozzarelli A. Amino Acids 47 163-173 (2015)
  9. Crystal structure of D-serine dehydratase from Escherichia coli. Urusova DV, Isupov MN, Antonyuk S, Kachalova GS, Obmolova G, Vagin AA, Lebedev AA, Burenkov GP, Dauter Z, Bartunik HD, Lamzin VS, Melik-Adamyan WR, Mueller TD, Schnackerz KD. Biochim Biophys Acta 1824 422-432 (2012)
  10. Glutamine 89 is a key residue in the allosteric modulation of human serine racemase activity by ATP. Canosa AV, Faggiano S, Marchetti M, Armao S, Bettati S, Bruno S, Percudani R, Campanini B, Mozzarelli A. Sci Rep 8 9016 (2018)
  11. Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for β-elimination function. Nelson DL, Applegate GA, Beio ML, Graham DL, Berkowitz DB. J Biol Chem 292 13986-14002 (2017)
  12. Catalytic mechanism of serine racemase from Dictyostelium discoideum. Ito T, Maekawa M, Hayashi S, Goto M, Hemmi H, Yoshimura T. Amino Acids 44 1073-1084 (2013)
  13. Crystal structures of open and closed forms of d-serine deaminase from Salmonella typhimurium - implications on substrate specificity and catalysis. Bharath SR, Bisht S, Savithri HS, Murthy MR. FEBS J 278 2879-2891 (2011)
  14. Metal ion dependency of serine racemase from Dictyostelium discoideum. Ito T, Murase H, Maekawa M, Goto M, Hayashi S, Saito H, Maki M, Hemmi H, Yoshimura T. Amino Acids 43 1567-1576 (2012)
  15. Structural and mutational studies on substrate specificity and catalysis of Salmonella typhimurium D-cysteine desulfhydrase. Bharath SR, Bisht S, Harijan RK, Savithri HS, Murthy MR. PLoS One 7 e36267 (2012)
  16. Role of zinc ion for catalytic activity in d-serine dehydratase from Saccharomyces cerevisiae. Ito T, Koga K, Hemmi H, Yoshimura T. FEBS J 279 612-624 (2012)
  17. Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target. Beato C, Pecchini C, Cocconcelli C, Campanini B, Marchetti M, Pieroni M, Mozzarelli A, Costantino G. J Enzyme Inhib Med Chem 31 645-652 (2016)
  18. Accelerated identification of serine racemase inhibitor from Centella asiatica. Rani K, Tyagi M, Mazumder M, Singh A, Shanmugam A, Dalal K, Pillai M, Samudrala G, Kumar S, Srinivasan A. Sci Rep 10 4640 (2020)
  19. Crystal structure of maize serine racemase with pyridoxal 5'-phosphate. Zou L, Song Y, Wang C, Sun J, Wang L, Cheng B, Fan J. Acta Crystallogr F Struct Biol Commun 72 165-171 (2016)
  20. Inhibition of serine and proline racemases by substrate-product analogues. Harty M, Nagar M, Atkinson L, Legay CM, Derksen DJ, Bearne SL. Bioorg Med Chem Lett 24 390-393 (2014)
  21. Modulating the function of human serine racemase and human serine dehydratase by protein engineering. Wang CY, Ku SC, Lee CC, Wang AH. Protein Eng Des Sel 25 741-749 (2012)
  22. Serine Racemase Expression by Striatal Neurons. Takagi S, Puhl MD, Anderson T, Balu DT, Coyle JT. Cell Mol Neurobiol 42 279-289 (2022)
  23. Site-directed mutagenesis of rice serine racemase: evidence that Glu219 and Asp225 mediate the effects of Mg2+ on the activity. Gogami Y, Kobayashi A, Ikeuchi T, Oikawa T. Chem Biodivers 7 1579-1590 (2010)
  24. Distribution of eukaryotic serine racemases in the bacterial domain and characterization of a representative protein in Roseobacter litoralis Och 149. Kubota T, Shimamura S, Kobayashi T, Nunoura T, Deguchi S. Microbiology (Reading) 162 53-61 (2016)
  25. Tailored Pyridoxal Probes Unravel Novel Cofactor-Dependent Targets and Antibiotic Hits in Critical Bacterial Pathogens. Pfanzelt M, Maher TE, Absmeier RM, Schwarz M, Sieber SA. Angew Chem Int Ed Engl 61 e202117724 (2022)
  26. Addressing the Conformational Flexibility of Serine Racemase by Combining Targeted Molecular Dynamics, Conformational Sampling and Docking Studies. Bruno A, Amori L, Costantino G. Mol Inform 30 317-328 (2011)
  27. D-Serine Metabolism and Its Importance in Development of Dictyostelium discoideum. Ito T, Hamauchi N, Hagi T, Morohashi N, Hemmi H, Sato YG, Saito T, Yoshimura T. Front Microbiol 9 784 (2018)
  28. Factors regulating serine racemase and d-amino acid oxidase expression in the mouse striatum. Takagi S, Balu DT, Coyle JT. Brain Res 1751 147202 (2021)
  29. Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg. Dyakin VV, Wisniewski TM, Lajtha A. Symmetry (Basel) 13 455 (2021)
  30. Conformational flexibility within the small domain of human serine racemase. Koulouris CR, Bax BD, Atack JR, Roe SM. Acta Crystallogr F Struct Biol Commun 76 65-73 (2020)
  31. Isolation and amino acid sequence of a dehydratase acting on d-erythro-3-hydroxyaspartate from Pseudomonas sp. N99, and its application in the production of optically active 3-hydroxyaspartate. Nagano H, Shibano K, Matsumoto Y, Yokota A, Wada M. Biosci Biotechnol Biochem 81 1156-1164 (2017)
  32. Involvement of C-terminal amino acids of a hyperthermophilic serine racemase in its thermostability. Murakami M, Saito M, Yokobori H, Nishimura K, Tanigawa M, Nagata Y. Extremophiles 22 99-107 (2018)


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