The structure of Pseudomonas mevalonii HMG-CoA reductase at 3.0 angstroms resolution
Abstract
The crystal structure of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase has been solved at 3.0 A resolution. The structure reveals a hexameric enzyme $\alpha 6)$ with 23 (D3) point group symmetry. The structure of a monomeric subunit is composed of a large and a small domain. The large domain is composed of a central 24 residue alpha helix surrounded by three walls of density, one of mixed alpha and beta structure, one of all alpha helical structure, and the third of a four stranded anti-parallel beta sheet with an alpha helix along one edge. The small domain is composed of a four stranded anti-parallel beta sheet with with alpha helices on one face of the sheet. Difference Fourier studies reveal the binding sites for the substrates HMG-CoA, CoA, mevalonate, NADH and NAD$\sp+.$ The structurally unique large domain is involved in the binding of HMG-CoA. The small domain is involved in binding of NADH and thus represents a new class of nucleotide binding domain. Two monomers associate to form a tight dimer with each monomer contributing to both active sites, which are found at the subunit interfaces. The hexameric structure is formed as a trimer of dimers with the dimer two-fold axis perpendicular to the three-fold axis.
Degree
Ph.D.
Advisors
Stauffacher, Purdue University.
Subject Area
Biophysics|Biochemistry
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