1jc4: Difference between revisions

Revision as of 14:21, 21 February 2008

Crystal Structure of Se-Met Methylmalonyl-CoA Epimerase

OverviewOverview

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.

About this StructureAbout this Structure

1JC4 is a Single protein structure of sequence from Propionibacterium freudenreichii subsp. shermanii with as ligand. Active as Methylmalonyl-CoA epimerase, with EC number 5.1.99.1 Full crystallographic information is available from OCA.

ReferenceReference

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. 2001 Jul 3;9(7):637-46. PMID:11470438

Page seeded by OCA on Thu Feb 21 13:21:06 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1jc4.jpg|left|200px]]<br /><applet load="1jc4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1jc4.jpg|left|200px]]<br /><applet load="1jc4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1jc4, resolution 2.00&Aring;" />
 '''Crystal Structure of Se-Met Methylmalonyl-CoA Epimerase'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-JC4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Methylmalonyl-CoA_epimerase Methylmalonyl-CoA epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.99.1 5.1.99.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JC4 OCA].
+JC4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Methylmalonyl-CoA_epimerase Methylmalonyl-CoA epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.99.1 5.1.99.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JC4 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Propionibacterium freudenreichii subsp. shermanii]]
 [[Category: Single protein]]
-[[Category: Baker, E.N.]]
+[[Category: Baker, E N.]]
-[[Category: Baker, H.M.]]
+[[Category: Baker, H M.]]
-[[Category: Carthy, A.A.Mc.]]
+[[Category: Carthy, A A.Mc.]]
-[[Category: Patchett, M.L.]]
+[[Category: Patchett, M L.]]
-[[Category: Shewry, S.C.]]
+[[Category: Shewry, S C.]]
 [[Category: SO4]]
 [[Category: methylmalonyl-coa]]
 [[Category: vicinal oxygen chelate superfamily]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 23:26:08 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:21:06 2008''