3VDQ

Crystal structure of alcaligenes faecalis D-3-hydroxybutyrate dehydrogenase in complex with NAD(+) and acetate

Replaces:  2ZEA

Summary for 3VDQ

• Entry DOI: 10.2210/pdb3vdq/pdb
• Related: 2YZ7 3VDR
• Descriptor: D-3-hydroxybutyrate dehydrogenase, ACETATE ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: nad dependent enzyme, hydroxybutyrate dehydrogenase, ketone bodies, oxidoreductase
• Biological source: Alcaligenes faecalis
• Total number of polymer chains: 4
• Total formula weight: 111587.62

Authors

Hoque, M.M.,Shimizu, S.,Hossain, M.T.,Yamamoto, T.,Suzuki, K.,Takenaka, A. (deposition date: 2012-01-06, release date: 2012-02-29, Last modification date: 2023-11-08)

Primary citation

Hoque, M.M.,Shimizu, S.,Hossain, M.T.,Yamamoto, T.,Imamura, S.,Suzuki, K.,Tsunoda, M.,Amano, H.,Sekiguchi, T.,Takenaka, A.
The structures of Alcaligenes faecalis D-3-hydroxybutyrate dehydrogenase before and after NAD+ and acetate binding suggest a dynamical reaction mechanism as a member of the SDR family.
Acta Crystallogr.,Sect.D, 64:496-505, 2008

PubMed Abstract: D-3-Hydroxybutyrate dehydrogenase, which catalyzes the reversible reaction between D-3-hydroxybutyrate and acetoacetate, has been classified into the short-chain dehydrogenase/reductase family and is a useful marker in the assay of diabetes mellitus and/or ketoacidosis. The enzyme from Alcaligenes faecalis was crystallized in the apo form and in the holo form with acetate as a substrate analogue. The crystal structures of both forms were determined at 2.2 angstroms resolution. The enzyme is a tetramer composed of four subunits assembled with noncrystallographic 222 point symmetry. Each subunit has two domains. The principal domain adopts the Rossmann fold essential for nucleotide binding, which is a common feature of the SDR family. NAD+ is bound in a large cleft in the domain. The pyrophosphate group of NAD+ is covered by the small additional domain, which is supported by two extended arms allowing domain movement. In the catalytic site, a water molecule is trapped by the catalytic Tyr155 and Ser142 residues in the vicinity of the bound NAD+ and acetate. The substrate analogue acetate is bound above the nicotinamide plane. A substrate (D-3-hydroxybutylate) bound model can reasonably be constructed by adding two C atoms into the void space between the water O atom and the methyl group of the acetate, suggesting a substrate-bound state before enzymatic reaction occurs. Based on these structural features, a reaction mechanism has been proposed.

PubMed: 18453685
DOI: 10.1107/S0907444908004009

Experimental method

X-RAY DIFFRACTION (2.2 Å)