3VDQ: Crystal Structure Of Alcaligenes Faecalis D-3-Hydroxybutyrate Dehydrogenase In Complex With Nad(+) And Acetate

Citation:
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.
PDB ID: 3VDQDownload
MMDB ID: 97660
PDB Deposition Date: 2012/1/6
Updated in MMDB: 2012/03
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3VDQ: tetrameric; determined by author and by software (PISA)
Molecular Components in 3VDQ
Label Count Molecule
Proteins (4 molecules)
4
D-3-hydroxybutyrate Dehydrogenase
Molecule annotation
Chemicals (14 molecules)
1
4
2
4
3
4
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.