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1jc5
From Proteopedia
(New page: 200px<br /><applet load="1jc5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jc5, resolution 2.20Å" /> '''Crystal Structure of...) |
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| - | [[Image:1jc5.jpg|left|200px]]<br /><applet load="1jc5" size=" | + | [[Image:1jc5.jpg|left|200px]]<br /><applet load="1jc5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jc5, resolution 2.20Å" /> | caption="1jc5, resolution 2.20Å" /> | ||
'''Crystal Structure of Native Methylmalonyl-CoA Epimerase'''<br /> | '''Crystal Structure of Native Methylmalonyl-CoA Epimerase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Methylmalonyl-CoA epimerase (MMCE) is an essential enzyme in | + | 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== | ==About this Structure== | ||
| - | 1JC5 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:// | + | 1JC5 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=1JC5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Propionibacterium freudenreichii subsp. shermanii]] | [[Category: Propionibacterium freudenreichii subsp. shermanii]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baker, E | + | [[Category: Baker, E N.]] |
| - | [[Category: Baker, H | + | [[Category: Baker, H M.]] |
| - | [[Category: Carthy, A | + | [[Category: Carthy, A A.Mc.]] |
| - | [[Category: Patchett, M | + | [[Category: Patchett, M L.]] |
| - | [[Category: Shewry, S | + | [[Category: Shewry, S C.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: epimerisation]] | [[Category: epimerisation]] | ||
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[[Category: vicinal oxygen chelate superfamily]] | [[Category: vicinal oxygen chelate superfamily]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:20:58 2008'' |
Revision as of 11:20, 21 February 2008
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Crystal Structure of Native Methylmalonyl-CoA Epimerase
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.
About this Structure
1JC5 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.
Reference
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 13:20:58 2008
