1MJ3

Crystal Structure Analysis of rat enoyl-CoA hydratase in complex with hexadienoyl-CoA

Summary for 1MJ3

• Entry DOI: 10.2210/pdb1mj3/pdb
• Related: 1DUB 1EY3 2DUB
• Descriptor: ENOYL-COA HYDRATASE, MITOCHONDRIAL, HEXANOYL-COENZYME A (3 entities in total)
• Functional Keywords: homohexamer, lyase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Mitochondrion matrix: P14604
• Total number of polymer chains: 6
• Total formula weight: 173915.15

Authors

Bell, A.F.,Feng, Y.,Hofstein, H.A.,Parikh, S.,Wu, J.,Rudolph, M.J.,Kisker, C.,Tonge, P.J. (deposition date: 2002-08-26, release date: 2002-09-24, Last modification date: 2024-02-14)

Primary citation

Bell, A.F.,Feng, Y.,Hofstein, H.A.,Parikh, S.,Wu, J.,Rudolph, M.J.,Kisker, C.,Whitty, A.,Tonge, P.J.
Stereoselectivity of Enoyl-CoA Hydratase Results from Preferential Activation of One of Two Bound Substrate Conformers
Chem.Biol., 9:1247-1255, 2002

PubMed Abstract: Enoyl-CoA hydratase catalyzes the hydration of trans-2-crotonyl-CoA to 3(S)- and 3(R)-hydroxybutyryl-CoA with a stereoselectivity (3(S)/3(R)) of 400,000 to 1. Importantly, Raman spectroscopy reveals that both the s-cis and s-trans conformers of the substrate analog hexadienoyl-CoA are bound to the enzyme, but that only the s-cis conformer is polarized. This selective polarization is an example of ground state strain, indicating the existence of catalytically relevant ground state destabilization arising from the selective complementarity of the enzyme toward the transition state rather than the ground state. Consequently, the stereoselectivity of the enzyme-catalyzed reaction results from the selective activation of one of two bound substrate conformers rather than from selective binding of a single conformer. These findings have important implications for inhibitor design and the role of ground state interactions in enzyme catalysis.

PubMed: 12445775
DOI: 10.1016/S1074-5521(02)00263-6

Experimental method

X-RAY DIFFRACTION (2.1 Å)