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PDBsum entry 1jc4
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of methylmalonyl-Coenzyme a epimerase from p. Shermanii: a novel enzymatic function on an ancient metal binding scaffold.
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Authors
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A.A.Mccarthy,
H.M.Baker,
S.C.Shewry,
M.L.Patchett,
E.N.Baker.
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Ref.
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Structure, 2001,
9,
637-646.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
637-646)
copyright 2001.
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Secondary reference #1
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Title
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Expression, Crystallization and preliminary characterization of methylmalonyl coenzyme a epimerase from propionibacterium shermanii.
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Authors
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A.A.Mccarthy,
H.M.Baker,
S.C.Shewry,
T.F.Kagawa,
E.Saafi,
M.L.Patchett,
E.N.Baker.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2001,
57,
706-708.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 Crystals of (a) native MMCE and (b) SeMet-substituted
MMCE.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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