PDBsum entry 1jc5

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Isomerase PDB id
Protein chains
(+ 0 more) 145 a.a. *
SO4 ×10
Waters ×128
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of native methylmalonyl-coa epimerase
Structure: Methylmalonyl-coa epimerase. Chain: a, b, c, d, e, f. Engineered: yes
Source: Propionibacterium freudenreichii subsp. Shermanii. Organism_taxid: 1752. Strain: subsp. Shermanii. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.248     R-free:   0.293
Authors: A.A.Mc Carthy,H.M.Baker,S.C.Shewry,M.L.Patchett,E.N.Baker
Key ref:
A.A.McCarthy et al. (2001). Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold. Structure, 9, 637-646. PubMed id: 11470438 DOI: 10.1016/S0969-2126(01)00622-0
07-Jun-01     Release date:   11-Jul-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q8VQN0  (Q8VQN0_PROFR) -  Methylmalonyl CoA epimerase
148 a.a.
145 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Methylmalonyl-CoA epimerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (R)-methylmalonyl-CoA = (S)-methylmalonyl-CoA
= (S)-methylmalonyl-CoA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     isomerase activity     2 terms  


    Added reference    
DOI no: 10.1016/S0969-2126(01)00622-0 Structure 9:637-646 (2001)
PubMed id: 11470438  
Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold.
A.A.McCarthy, H.M.Baker, S.C.Shewry, M.L.Patchett, E.N.Baker.
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. CONCLUSIONS: 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.
  Selected figure(s)  
Figure 4.
Figure 4. The Metal Binding Site in MMCE(a) The difference electron density peak for the bound Co2+ ion is shown, in coordinating distance of the side chains of His12, Gln65, His91, and Glu141. Virtually no movement of these coordinating groups occurs on metal complexation to the apo-protein.(b) The metal sites of MMCE and GLO are superimposed using only the Ca atoms of the two proteins for superposition. For MMCE, the polypeptide backbone is in gray, with side chains and the Co2+ ion in blue; for GLO, the polypeptide backbone is in black, with side chains in red (monomer A) and gold (monomer B), and the Zn2+ ion in red

  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 637-646) copyright 2001.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
20696392 J.Zheng, C.A.Taylor, S.K.Piasecki, and A.T.Keatinge-Clay (2010).
Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase.
  Structure, 18, 913-922.
PDB codes: 3mjc 3mje 3mjs 3mjt 3mjv
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
19731367 L.Shi, P.Gao, X.X.Yan, and D.C.Liang (2009).
Crystal structure of a putative methylmalonyl-coenzyme a epimerase from Thermoanaerobacter tengcongensis at 2.0 A resolution.
  Proteins, 77, 994-999.
PDB code: 3gm5
19101977 X.Wu, P.M.Flatt, H.Xu, and T.Mahmud (2009).
Biosynthetic Gene Cluster of Cetoniacytone A, an Unusual Aminocyclitol from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419.
  Chembiochem, 10, 304-314.  
18604568 C.Andreini, I.Bertini, G.Cavallaro, G.L.Holliday, and J.M.Thornton (2008).
Metal ions in biological catalysis: from enzyme databases to general principles.
  J Biol Inorg Chem, 13, 1205-1218.  
18645235 C.Dumas, and A.van der Lee (2008).
Macromolecular structure solution by charge flipping.
  Acta Crystallogr D Biol Crystallogr, 64, 864-873.  
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
18791196 I.Mulako, J.M.Farrant, H.Collett, and N.Illing (2008).
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.
  J Exp Bot, 59, 3885-3901.  
  18533363 N.Sukdeo, and J.F.Honek (2008).
Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal.
  Drug Metabol Drug Interact, 23, 29-50.  
18819910 T.J.Erb, J.Rétey, G.Fuchs, and B.E.Alber (2008).
Ethylmalonyl-CoA mutase from Rhodobacter sphaeroides defines a new subclade of coenzyme B12-dependent acyl-CoA mutases.
  J Biol Chem, 283, 32283-32293.  
16076399 F.Ferrè, G.Ausiello, A.Zanzoni, and M.Helmer-Citterich (2005).
Functional annotation by identification of local surface similarities: a novel tool for structural genomics.
  BMC Bioinformatics, 6, 194.  
16121186 F.H.Vaillancourt, E.Yeh, D.A.Vosburg, S.E.O'Connor, and C.T.Walsh (2005).
Cryptic chlorination by a non-haem iron enzyme during cyclopropyl amino acid biosynthesis.
  Nature, 436, 1191-1194.  
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
15752362 J.Kühnl, T.Bobik, J.B.Procter, C.Burmeister, J.Höppner, I.Wilde, K.Lüersen, A.E.Torda, R.D.Walter, and E.Liebau (2005).
Functional analysis of the methylmalonyl-CoA epimerase from Caenorhabditis elegans.
  FEBS J, 272, 1465-1477.  
12660999 R.G.Zhang, N.Duke, R.Laskowski, E.Evdokimova, T.Skarina, A.Edwards, A.Joachimiak, and A.Savchenko (2003).
Conserved protein YecM from Escherichia coli shows structural homology to metal-binding isomerases and oxygenases.
  Proteins, 51, 311-314.
PDB code: 1k4n
12121648 T.W.Martin, Z.Dauter, Y.Devedjiev, P.Sheffield, F.Jelen, M.He, D.H.Sherman, J.Otlewski, Z.S.Derewenda, and U.Derewenda (2002).
Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.
  Structure, 10, 933-942.
PDB codes: 1kll 1kmz
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.