1DUB

2-ENOYL-COA HYDRATASE, DATA COLLECTED AT 100 K, PH 6.5

Summary for 1DUB

• Entry DOI: 10.2210/pdb1dub/pdb
• Descriptor: 2-ENOYL-COA HYDRATASE, ACETOACETYL-COENZYME A (3 entities in total)
• Functional Keywords: beta-oxidation, coa, crotonase, enoyl-coa hydratase, fatty acid metabolism, lyase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Mitochondrion matrix: P14604
• Total number of polymer chains: 6
• Total formula weight: 174187.12

Authors

Wierenga, R.K.,Engel, C.K. (deposition date: 1996-06-10, release date: 1997-07-07, Last modification date: 2024-02-07)

Primary citation

Engel, C.K.,Mathieu, M.,Zeelen, J.P.,Hiltunen, J.K.,Wierenga, R.K.
Crystal structure of enoyl-coenzyme A (CoA) hydratase at 2.5 angstroms resolution: a spiral fold defines the CoA-binding pocket.
EMBO J., 15:5135-5145, 1996

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

PubMed: 8895557

Experimental method

X-RAY DIFFRACTION (2.5 Å)