1req
From Proteopedia
(New page: 200px<br /><applet load="1req" size="450" color="white" frame="true" align="right" spinBox="true" caption="1req, resolution 2.0Å" /> '''METHYLMALONYL-COA MUT...) |
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| - | [[Image:1req.gif|left|200px]]<br /><applet load="1req" size=" | + | [[Image:1req.gif|left|200px]]<br /><applet load="1req" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1req, resolution 2.0Å" /> | caption="1req, resolution 2.0Å" /> | ||
'''METHYLMALONYL-COA MUTASE'''<br /> | '''METHYLMALONYL-COA MUTASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND. The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta | + | BACKGROUND. The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta heterodimer of 150 kDa, is a member of a class of enzymes that uses coenzyme B12 (adenosylcobalamin) as a cofactor. The enzyme induces the formation of an adenosyl radical from the cofactor. This radical then initiates a free-radical rearrangement of its substrate, succinyl-CoA, to methylmalonyl-CoA. RESULTS. Reported here is the crystal structure at 2 A resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in complex with coenzyme B12 and with the partial substrate desulpho-CoA (lacking the succinyl group and the sulphur atom of the substrate). The coenzyme is bound by a domain which shares a similar fold to those of flavodoxin and the B12-binding domain of methylcobalamin-dependent methionine synthase. The cobalt atom is coordinated, via a long bond, to a histidine from the protein. The partial substrate is bound along the axis of a (beta/alpha)8 TIM barrel domain. CONCLUSIONS. The histidine-cobalt distance is very long (2.5 A compared with 1.95-2.2 A in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the metal-carbon bond of the cofactor and favour the formation of the initial radical species. The active site is deeply buried, and the only access to it is through a narrow tunnel along the axis of the TIM barrel domain. |
==About this Structure== | ==About this Structure== | ||
| - | 1REQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii] with B12, DCA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methylmalonyl-CoA_mutase Methylmalonyl-CoA mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.2 5.4.99.2] Full crystallographic information is available from [http:// | + | 1REQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii] with <scene name='pdbligand=B12:'>B12</scene>, <scene name='pdbligand=DCA:'>DCA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methylmalonyl-CoA_mutase Methylmalonyl-CoA mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.2 5.4.99.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1REQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Propionibacterium freudenreichii subsp. shermanii]] | [[Category: Propionibacterium freudenreichii subsp. shermanii]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Evans, P | + | [[Category: Evans, P R.]] |
[[Category: Mancia, F.]] | [[Category: Mancia, F.]] | ||
[[Category: B12]] | [[Category: B12]] | ||
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[[Category: mutase]] | [[Category: mutase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:50:04 2008'' |
Revision as of 12:50, 21 February 2008
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METHYLMALONYL-COA MUTASE
Overview
BACKGROUND. The enzyme methylmalonyl-coenzyme A (CoA) mutase, an alphabeta heterodimer of 150 kDa, is a member of a class of enzymes that uses coenzyme B12 (adenosylcobalamin) as a cofactor. The enzyme induces the formation of an adenosyl radical from the cofactor. This radical then initiates a free-radical rearrangement of its substrate, succinyl-CoA, to methylmalonyl-CoA. RESULTS. Reported here is the crystal structure at 2 A resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in complex with coenzyme B12 and with the partial substrate desulpho-CoA (lacking the succinyl group and the sulphur atom of the substrate). The coenzyme is bound by a domain which shares a similar fold to those of flavodoxin and the B12-binding domain of methylcobalamin-dependent methionine synthase. The cobalt atom is coordinated, via a long bond, to a histidine from the protein. The partial substrate is bound along the axis of a (beta/alpha)8 TIM barrel domain. CONCLUSIONS. The histidine-cobalt distance is very long (2.5 A compared with 1.95-2.2 A in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the metal-carbon bond of the cofactor and favour the formation of the initial radical species. The active site is deeply buried, and the only access to it is through a narrow tunnel along the axis of the TIM barrel domain.
About this Structure
1REQ is a Protein complex structure of sequences from Propionibacterium freudenreichii subsp. shermanii with , and as ligands. Active as Methylmalonyl-CoA mutase, with EC number 5.4.99.2 Full crystallographic information is available from OCA.
Reference
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution., Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR, Structure. 1996 Mar 15;4(3):339-50. PMID:8805541
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