1s9c
From Proteopedia
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Crystal structure analysis of the 2-enoyl-CoA hydratase 2 domain of human peroxisomal multifunctional enzyme type 2
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Overview
2-Enoyl-CoA hydratase 2 is the middle part of the mammalian peroxisomal, multifunctional enzyme type 2 (MFE-2), which is known to be important in, the beta-oxidation of very-long-chain and alpha-methyl-branched fatty, acids as well as in the synthesis of bile acids. Here, we present the, crystal structure of the hydratase 2 from the human MFE-2 to 3A, resolution. The three-dimensional structure resembles the recently solved, crystal structure of hydratase 2 from the yeast, Candida tropicalis, MFE-2, having a two-domain subunit structure with a C-domain complete hot-dog, fold housing the active site, and an N-domain incomplete hot-dog fold, housing the cavity for the aliphatic acyl part of the substrate molecule., The ability of human hydratase 2 to utilize such bulky compounds which are, not physiological substrates for the fungal ortholog, e.g. CoA esters of, C26 fatty acids, pristanic acid and di/trihydroxycholestanoic acids, is, explained by a large hydrophobic cavity formed upon the movements of the, extremely mobile loops I-III in the N-domain. In the unliganded form of, human hydratase 2, however, the loop I blocks the entrance of fatty, enoyl-CoAs with chain-length >C8. Therefore, we expect that upon binding, of substrates bulkier than C8, the loop I gives way, contemporaneously, causing a secondary effect in the CoA-binding pocket and/or active site, required for efficient hydration reaction. This structural feature would, explain the inactivity of human hydratase 2 towards short-chain, substrates. The solved structure is also used as a tool for analyzing the, various inactivating mutations, identified among others in MFE-2-deficient, patients. Since hydratase 2 is the last functional unit of mammalian MFE-2, whose structure has been solved, the organization of the functional units, in the biologically active full-length enzyme is also discussed.
Disease
Known disease associated with this structure: D-bifunctional protein deficiency OMIM:[601860]
About this Structure
1S9C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2., Koski KM, Haapalainen AM, Hiltunen JK, Glumoff T, J Mol Biol. 2005 Feb 4;345(5):1157-69. Epub 2004 Dec 10. PMID:15644212
Page seeded by OCA on Mon Nov 12 19:11:15 2007
