1xx4
From Proteopedia
(New page: 200px<br /><applet load="1xx4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xx4, resolution 2.20Å" /> '''Crystal Structure of...) |
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| - | [[Image:1xx4.jpg|left|200px]]<br /><applet load="1xx4" size=" | + | [[Image:1xx4.jpg|left|200px]]<br /><applet load="1xx4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xx4, resolution 2.20Å" /> | caption="1xx4, resolution 2.20Å" /> | ||
'''Crystal Structure of Rat Mitochondrial 3,2-Enoyl-CoA'''<br /> | '''Crystal Structure of Rat Mitochondrial 3,2-Enoyl-CoA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Two monofunctional Delta(3), Delta(2)-enoyl-CoA isomerases, one in | + | Two monofunctional Delta(3), Delta(2)-enoyl-CoA isomerases, one in mitochondria (mECI) and the other in both mitochondria and peroxisomes (pECI), belong to the low-similarity isomerase/hydratase superfamily. Both enzymes catalyze the movement of a double bond from C3 to C2 of an unsaturated acyl-CoA substrate for re-entry into the beta-oxidation pathway. Mutagenesis has shown that Glu165 of rat mECI is involved in catalysis; however, the putative catalytic residue in yeast pECI, Glu158, is not conserved in mECI. To elucidate whether Glu165 of mECI is correctly positioned for catalysis, the crystal structure of rat mECI has been solved. Crystal packing suggests the enzyme is trimeric, in contrast to other members of the superfamily, which appear crystallographically to be dimers of trimers. The polypeptide fold of mECI, like pECI, belongs to a subset of this superfamily in which the C-terminal domain of a given monomer interacts with its own N-terminal domain. This differs from that of crotonase and 1,4-dihydroxy-2-naphtoyl-CoA synthase, whose C-terminal domains are involved in domain swapping with an adjacent monomer. The structure confirms Glu165 as the putative catalytic acid/base, positioned to abstract the pro-R proton from C2 and reprotonate at C4 of the acyl chain. The large tunnel-shaped active site cavity observed in the mECI structure explains the relative substrate promiscuity in acyl-chain length and stereochemistry. Comparison with the crystal structure of pECI suggests the catalytic residues from both enzymes are spatially conserved but not in their primary structures, providing a powerful reminder of how catalytic residues cannot be determined solely by sequence alignments. |
==About this Structure== | ==About this Structure== | ||
| - | 1XX4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with PO4, ZN and BAM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dodecenoyl-CoA_isomerase Dodecenoyl-CoA isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.3.8 5.3.3.8] Full crystallographic information is available from [http:// | + | 1XX4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=BAM:'>BAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dodecenoyl-CoA_isomerase Dodecenoyl-CoA isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.3.8 5.3.3.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XX4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Hubbard, P | + | [[Category: Hubbard, P A.]] |
| - | [[Category: Kim, J | + | [[Category: Kim, J J.]] |
[[Category: Schulz, H.]] | [[Category: Schulz, H.]] | ||
[[Category: Yu, W.]] | [[Category: Yu, W.]] | ||
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[[Category: domain swapped]] | [[Category: domain swapped]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:59:32 2008'' |
Revision as of 13:59, 21 February 2008
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Crystal Structure of Rat Mitochondrial 3,2-Enoyl-CoA
Overview
Two monofunctional Delta(3), Delta(2)-enoyl-CoA isomerases, one in mitochondria (mECI) and the other in both mitochondria and peroxisomes (pECI), belong to the low-similarity isomerase/hydratase superfamily. Both enzymes catalyze the movement of a double bond from C3 to C2 of an unsaturated acyl-CoA substrate for re-entry into the beta-oxidation pathway. Mutagenesis has shown that Glu165 of rat mECI is involved in catalysis; however, the putative catalytic residue in yeast pECI, Glu158, is not conserved in mECI. To elucidate whether Glu165 of mECI is correctly positioned for catalysis, the crystal structure of rat mECI has been solved. Crystal packing suggests the enzyme is trimeric, in contrast to other members of the superfamily, which appear crystallographically to be dimers of trimers. The polypeptide fold of mECI, like pECI, belongs to a subset of this superfamily in which the C-terminal domain of a given monomer interacts with its own N-terminal domain. This differs from that of crotonase and 1,4-dihydroxy-2-naphtoyl-CoA synthase, whose C-terminal domains are involved in domain swapping with an adjacent monomer. The structure confirms Glu165 as the putative catalytic acid/base, positioned to abstract the pro-R proton from C2 and reprotonate at C4 of the acyl chain. The large tunnel-shaped active site cavity observed in the mECI structure explains the relative substrate promiscuity in acyl-chain length and stereochemistry. Comparison with the crystal structure of pECI suggests the catalytic residues from both enzymes are spatially conserved but not in their primary structures, providing a powerful reminder of how catalytic residues cannot be determined solely by sequence alignments.
About this Structure
1XX4 is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Active as Dodecenoyl-CoA isomerase, with EC number 5.3.3.8 Full crystallographic information is available from OCA.
Reference
Domain swapping in the low-similarity isomerase/hydratase superfamily: the crystal structure of rat mitochondrial Delta3, Delta2-enoyl-CoA isomerase., Hubbard PA, Yu W, Schulz H, Kim JJ, Protein Sci. 2005 Jun;14(6):1545-55. Epub 2005 May 9. PMID:15883186
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