PMID- 11470438
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20190915
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 9
IP  - 7
DP  - 2001 Jul 3
TI  - Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a 
      novel enzymatic function on an ancient metal binding scaffold.
PG  - 637-46
AB  - 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.
FAU - McCarthy, A A
AU  - McCarthy AA
AD  - School of Biological Sciences, University of Auckland, Auckland, New Zealand.
FAU - Baker, H M
AU  - Baker HM
FAU - Shewry, S C
AU  - Shewry SC
FAU - Patchett, M L
AU  - Patchett ML
FAU - Baker, E N
AU  - Baker EN
LA  - eng
SI  - PDB/1JC4
SI  - PDB/1JC5
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Metals)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - EC 5.1.99.1 (methylmalonyl-coenzyme A racemase)
SB  - IM
MH  - Binding Sites
MH  - Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Dimerization
MH  - Enzyme Stability
MH  - Evolution, Molecular
MH  - Metals/*metabolism
MH  - Models, Molecular
MH  - Propionibacterium/*enzymology
MH  - Protein Conformation
MH  - Racemases and Epimerases/*chemistry/*metabolism
EDAT- 2001/07/27 10:00
MHDA- 2001/10/05 10:01
CRDT- 2001/07/27 10:00
PHST- 2001/07/27 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/07/27 10:00 [entrez]
AID - S0969212601006220 [pii]
AID - 10.1016/s0969-2126(01)00622-0 [doi]
PST - ppublish
SO  - Structure. 2001 Jul 3;9(7):637-46. doi: 10.1016/s0969-2126(01)00622-0.