Crystal structure of enoyl-coenzyme A (CoA) hydratase at 2.5 angstroms resolution: a spiral fold defines the CoA-binding pocket.

摘要: The crystal structure of rat liver mitochondrial enoyl-coenzyme A (CoA) hydratase complexed with the potent inhibitor acetoacetyl-CoA has been refined at 2.5 angstroms resolution. This enzyme catalyses reversible addition water to alpha,beta-unsaturated enoyl-CoA thioesters, nearly diffusion-controlled reaction rates for best substrates. Enoyl-CoA is a hexamer six identical subunits 161 kDa molecular mass complex. dimer trimers. monomer folded into right-handed spiral four turns, followed by two small domains which are involved in trimerization. Each turn consists beta-strands and an alpha-helix. mechanism hydratase/dehydratase follows syn-stereochemistry, preference that opposite nonenzymatic reaction. active-site architecture agrees this stereochemistry. It confirms importance Glu164 as catalytic acid providing alpha-proton during also shows Glu144 base activation molecule comparison unliganded liganded active site within same form subunit. bound between glutamates could serve activated catalysis.