2et6
From Proteopedia
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(3R)-Hydroxyacyl-CoA Dehydrogenase Domain of Candida tropicalis Peroxisomal Multifunctional Enzyme Type 2
Overview
(3R)-hydroxyacyl-CoA dehydrogenase is part of multifunctional enzyme type, 2 (MFE-2) of peroxisomal fatty acid beta-oxidation. The MFE-2 protein from, yeasts contains in the same polypeptide chain two dehydrogenases (A and, B), which possess difference in substrate specificity. The crystal, structure of Candida tropicalis (3R)-hydroxyacyl-CoA dehydrogenase AB, heterodimer, consisting of dehydrogenase A and B, determined at the, resolution of 2.2A, shows overall similarity with the prototypic, counterpart from rat, but also important differences that explain the, substrate specificity differences observed. Docking studies suggest that, dehydrogenase A binds the hydrophobic fatty acyl chain of a, medium-chain-length ((3R)-OH-C10) substrate as bent into the binding, pocket, whereas the short-chain substrates are dislocated by two, mechanisms: (i) a short-chain-length 3-hydroxyacyl group ((3R)-OH-C4) does, not reach the hydrophobic contacts needed for anchoring the substrate into, the active site; and (ii) Leu44 in the loop above the NAD(+) cofactor, attracts short-chain-length substrates away from the active site., Dehydrogenase B, which can use a (3R)-OH-C4 substrate, has a more shallow, binding pocket and the substrate is correctly placed for catalysis. Based, on the current structure, and together with the structure of the, 2-enoyl-CoA hydratase 2 unit of yeast MFE-2 it becomes obvious that in, yeast and mammalian MFE-2s, despite basically identical functional, domains, the assembly of these domains into a mature, dimeric, multifunctional enzyme is very different.
About this Structure
2ET6 is a Single protein structure of sequence from Candida tropicalis. Full crystallographic information is available from OCA.
Reference
Crystal structure of yeast peroxisomal multifunctional enzyme: structural basis for substrate specificity of (3R)-hydroxyacyl-CoA dehydrogenase units., Ylianttila MS, Pursiainen NV, Haapalainen AM, Juffer AH, Poirier Y, Hiltunen JK, Glumoff T, J Mol Biol. 2006 May 19;358(5):1286-95. Epub 2006 Mar 30. PMID:16574148
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