1jc5 › Citations

Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold.

McCarthy AA, Baker HM, Shewry SC, Patchett ML, Baker EN
Structure 9 637-46 (2001)
Cited: 35 times
EuropePMC logo PMID: 11470438

Abstract

Background

Methylmalonyl-CoA epimerase (MMCE) is an essential enzyme in the breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine, and methionine. Present in many bacteria and in animals, it catalyzes the conversion of (2R)-methylmalonyl-CoA to (2S)-methylmalonyl-CoA, the substrate for the B12-dependent enzyme, methylmalonyl-CoA mutase. Defects in this pathway can result in severe acidosis and cause damage to the central nervous system in humans.

Results

The crystal structure of MMCE from Propionibacterium shermanii has been determined at 2.0 A resolution. The MMCE monomer is folded into two tandem betaalphabetabetabeta modules that pack edge-to-edge to generate an 8-stranded beta sheet. Two monomers then pack back-to-back to create a tightly associated dimer. In each monomer, the beta sheet curves around to create a deep cleft, in the floor of which His12, Gln65, His91, and Glu141 provide a binding site for a divalent metal ion, as shown by the binding of Co2+. Modeling 2-methylmalonate into the active site identifies two glutamate residues as the likely essential bases for the epimerization reaction.

Conclusion

The betaalphabetabetabeta modules of MMCE correspond with those found in several other proteins, including bleomycin resistance protein, glyoxalase I, and a family of extradiol dioxygenases. Differences in connectivity are consistent with the evolution of these very different proteins from a common precursor by mechanisms of gene duplication and domain swapping. The metal binding residues also align precisely, and striking structural similarities between MMCE and glyoxalase I suggest common mechanisms in their respective epimerization and isomerization reactions.

Articles - 1jc5 mentioned but not cited (5)

  1. Functional annotation by identification of local surface similarities: a novel tool for structural genomics. Ferrè F, Ausiello G, Zanzoni A, Helmer-Citterich M. BMC Bioinformatics 6 194 (2005)
  2. Toxoflavin lyase requires a novel 1-His-2-carboxylate facial triad. Fenwick MK, Philmus B, Begley TP, Ealick SE. Biochemistry 50 1091-1100 (2011)
  3. Resistance to Enediyne Antitumor Antibiotics by Sequestration. Chang CY, Yan X, Crnovcic I, Annaval T, Chang C, Nocek B, Rudolf JD, Yang D, Hindra, Babnigg G, Joachimiak A, Phillips GN, Shen B. Cell Chem Biol 25 1075-1085.e4 (2018)
  4. Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. Heuberger K, Bailey HJ, Burda P, Chaikuad A, Krysztofinska E, Suormala T, Bürer C, Lutz S, Fowler B, Froese DS, Yue WW, Baumgartner MR. Biochim Biophys Acta Mol Basis Dis 1865 1265-1272 (2019)
  5. Utilization of cobalamin is ubiquitous in early-branching fungal phyla. Orłowska M, Steczkiewicz K, Muszewska A. Genome Biol Evol 13 evab043 (2021)


Reviews citing this publication (4)

  1. The ins and outs of ring-cleaving dioxygenases. Vaillancourt FH, Bolin JT, Eltis LD. Crit Rev Biochem Mol Biol 41 241-267 (2006)
  2. The genomic enzymology of antibiotic resistance. Morar M, Wright GD. Annu Rev Genet 44 25-51 (2010)
  3. The Human Glyoxalase Gene Family in Health and Disease. Farrera DO, Galligan JJ. Chem Res Toxicol 35 1766-1776 (2022)
  4. Racemases and epimerases operating through a 1,1-proton transfer mechanism: reactivity, mechanism and inhibition. Lloyd MD, Yevglevskis M, Nathubhai A, James TD, Threadgill MD, Woodman TJ. Chem Soc Rev 50 5952-5984 (2021)

Articles citing this publication (26)

  1. Metal ions in biological catalysis: from enzyme databases to general principles. Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM. J Biol Inorg Chem 13 1205-1218 (2008)
  2. Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis. Vaillancourt FH, Yeh E, Vosburg DA, O'Connor SE, Walsh CT. Nature 436 1191-1194 (2005)
  3. Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase. Zheng J, Taylor CA, Piasecki SK, Keatinge-Clay AT. Structure 18 913-922 (2010)
  4. Catalysing new reactions during evolution: economy of residues and mechanism. Bartlett GJ, Borkakoti N, Thornton JM. J Mol Biol 331 829-860 (2003)
  5. Structural variation in bacterial glyoxalase I enzymes: investigation of the metalloenzyme glyoxalase I from Clostridium acetobutylicum. Suttisansanee U, Lau K, Lagishetty S, Rao KN, Swaminathan S, Sauder JM, Burley SK, Honek JF. J Biol Chem 286 38367-38374 (2011)
  6. Using reaction mechanism to measure enzyme similarity. O'Boyle NM, Holliday GL, Almonacid DE, Mitchell JB. J Mol Biol 368 1484-1499 (2007)
  7. Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria. Dobson CM, Gradinger A, Longo N, Wu X, Leclerc D, Lerner-Ellis J, Lemieux M, Belair C, Watkins D, Rosenblatt DS, Gravel RA. Mol Genet Metab 88 327-333 (2006)
  8. Structural insight into gene duplication, gene fusion and domain swapping in the evolution of PLP-independent amino acid racemases. Liu L, Iwata K, Yohda M, Miki K. FEBS Lett 528 114-118 (2002)
  9. Biosynthetic gene cluster of cetoniacytone A, an unusual aminocyclitol from the endosymbiotic Bacterium Actinomyces sp. Lu 9419. Wu X, Flatt PM, Xu H, Mahmud T. Chembiochem 10 304-314 (2009)
  10. Functional analysis of the methylmalonyl-CoA epimerase from Caenorhabditis elegans. Kühnl J, Bobik T, Procter JB, Burmeister C, Höppner J, Wilde I, Lüersen K, Torda AE, Walter RD, Liebau E. FEBS J 272 1465-1477 (2005)
  11. The catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface. Bhaumik P, Schmitz W, Hassinen A, Hiltunen JK, Conzelmann E, Wierenga RK. J Mol Biol 367 1145-1161 (2007)
  12. Epimerase (Msed_0639) and mutase (Msed_0638 and Msed_2055) convert (S)-methylmalonyl-coenzyme A (CoA) to succinyl-CoA in the Metallosphaera sedula 3-hydroxypropionate/4-hydroxybutyrate cycle. Han Y, Hawkins AS, Adams MW, Adams MW, Kelly RM. Appl Environ Microbiol 78 6194-6202 (2012)
  13. Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein. Martin TW, Dauter Z, Devedjiev Y, Sheffield P, Jelen F, He M, Sherman DH, Otlewski J, Derewenda ZS, Derewenda U. Structure 10 933-942 (2002)
  14. Whole-Genome Identification and Expression Pattern of the Vicinal Oxygen Chelate Family in Rapeseed (Brassica napus L.). Liang Y, Wan N, Cheng Z, Mo Y, Liu B, Liu H, Raboanatahiry N, Yin Y, Li M. Front Plant Sci 8 745 (2017)
  15. Expression of Xhdsi-1VOC, a novel member of the vicinal oxygen chelate (VOC) metalloenzyme superfamily, is up-regulated in leaves and roots during desiccation in the resurrection plant Xerophyta humilis (Bak) Dur and Schinz. Mulako I, Farrant JM, Collett H, Illing N. J Exp Bot 59 3885-3901 (2008)
  16. Convergent Evolution of a Promiscuous 3-Hydroxypropionyl-CoA Dehydratase/Crotonyl-CoA Hydratase in Crenarchaeota and Thaumarchaeota. Liu L, Brown PC, Könneke M, Huber H, König S, Berg IA. mSphere 6 e01079-20 (2021)
  17. A study on the chiral inversion of mandelic acid in humans. Yevglevskis M, Bowskill CR, Chan CC, Heng JH, Threadgill MD, Woodman TJ, Lloyd MD. Org Biomol Chem 12 6737-6744 (2014)
  18. Conserved protein YecM from Escherichia coli shows structural homology to metal-binding isomerases and oxygenases. Zhang RG, Duke N, Laskowski R, Evdokimova E, Skarina T, Edwards A, Joachimiak A, Savchenko A. Proteins 51 311-314 (2003)
  19. Crystal structure of a putative methylmalonyl-coenzyme A epimerase from Thermoanaerobacter tengcongensis at 2.0 A resolution. Shi L, Gao P, Yan XX, Liang DC. Proteins 77 994-999 (2009)
  20. Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family. Chirgadze YN, Boshkova EA, Battaile KP, Mendes VG, Lam R, Chan TSY, Romanov V, Pai EF, Chirgadze NY. J Biomol Struct Dyn 36 376-386 (2018)
  21. Expression, purification, characterization and in silico analysis of newly isolated hydrocarbon degrading bleomycin resistance dioxygenase. Sharma V, Kumar R, Kumar R, Kumar R, Sharma VK, Yadav AK, Tiirola M, Sharma PK. Mol Biol Rep 47 533-544 (2020)
  22. Novel approach for structural identification of protein family: glyoxalase I. Kargatov AM, Boshkova EA, Chirgadze YN. J Biomol Struct Dyn 36 2699-2712 (2018)
  23. Computational analysis on two putative mitochondrial protein-coding genes from the Emydura subglobosa genome: A functional annotation approach. Yu M. PLoS One 17 e0268031 (2022)
  24. Genomic discovery and structural dissection of a novel type of polymorphic toxin system in gram-positive bacteria. Li H, Tan Y, Zhang D. Comput Struct Biotechnol J 20 4517-4531 (2022)
  25. Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase. Chen M, Guo Z, Sun J, Tang W, Wang M, Tang Y, Li P, Wu B, Chen Y. Acta Pharm Sin B 13 765-774 (2023)
  26. β-Strand-mediated interactions of protein domains. Bhat AS, Kinch LN, Grishin NV. Proteins 88 1513-1527 (2020)


Related citations provided by authors (1)

  1. Expression, Crystallization and Preliminary Characterization of Methylmalonyl Coenzyme A Epimerase from Propionibacterium shermanii. Mc Carthy AA, Baker HM, Shewry SC, Kagawa TF, Saafi E, Patchett ML, Baker EN Acta Crystallogr. D Biol. Crystallogr. 57 706-708 (2001)

Quick links