PDBsum entry 3cxr

Oxidoreductase

PDB id: 3cxr

Contents

Protein chain

260 a.a. *

Waters ×130

* Residue conservation analysis

PDB id:

3cxr

Name:

Oxidoreductase

Title:

Crystal structure of gluconate 5-dehydrogase from streptococcus suis type 2

Structure:

Dehydrogenase with different specificities. Chain: a. Synonym: related to short-chain alcohol dehydrogenase. Engineered: yes

Source:

Streptococcus suis. Organism_taxid: 391295. Strain: 05hah33. Gene: ssu05_1225, idno. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.192 R-free: 0.208

Authors:

H.Peng,F.Gao,Q.Zhang,Y.Liu,G.F.Gao

Key ref:

Q.Zhang et al. (2009). Structural insight into the catalytic mechanism of gluconate 5-dehydrogenase from Streptococcus suis: Crystal structures of the substrate-free and quaternary complex enzymes. Protein Sci, 18, 294-303. PubMed id: 19177572 DOI: 10.1002/pro.32

Date:

25-Apr-08 Release date: 17-Mar-09

Protein chain

A4VVQ2  (A4VVQ2_STRSY) -

Enzyme reactions

• Enzyme class: E.C.1.1.1.69 - gluconate 5-dehydrogenase.
• Reaction:
  1. D-gluconate + NADP⁺ = 5-dehydro-D-gluconate + NADPH + H⁺
  2. D-gluconate + NAD⁺ = 5-dehydro-D-gluconate + NADH + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1002/pro.32

Protein Sci 18:294-303 (2009)

PubMed id: 19177572

Structural insight into the catalytic mechanism of gluconate 5-dehydrogenase from Streptococcus suis: Crystal structures of the substrate-free and quaternary complex enzymes.

Q.Zhang, H.Peng, F.Gao, Y.Liu, H.Cheng, J.Thompson, G.F.Gao.

ABSTRACT

Gluconate 5-dehydrogenase (Ga5DH) is an NADP(H)-dependent enzyme that catalyzes a reversible oxidoreduction reaction between D-gluconate and 5-keto-D-gluconate, thereby regulating the flux of this important carbon and energy source in bacteria. Despite the considerable amount of physiological and biochemical knowledge of Ga5DH, there is little physical or structural information available for this enzyme. To this end, we herein report the crystal structures of Ga5DH from pathogenic Streptococcus suis serotype 2 in both substrate-free and liganded (NADP(+)/D-gluconate/metal ion) quaternary complex forms at 2.0 A resolution. Structural analysis reveals that Ga5DH adopts a protein fold similar to that found in members of the short chain dehydrogenase/reductase (SDR) family, while the enzyme itself represents a previously uncharacterized member of this family. In solution, Ga5DH exists as a tetramer that comprised four identical approximately 29 kDa subunits. The catalytic site of Ga5DH shows considerable architectural similarity to that found in other enzymes of the SDR family, but the S. suis protein contains an additional residue (Arg104) that plays an important role in the binding and orientation of substrate. The quaternary complex structure provides the first clear crystallographic evidence for the role of a catalytically important serine residue and also reveals an amino acid tetrad RSYK that differs from the SYK triad found in the majority of SDR enzymes. Detailed analysis of the crystal structures reveals important contributions of Ca(2+) ions to active site formation and of specific residues at the C-termini of subunits to tetramer assembly. Because Ga5DH is a potential target for therapy, our findings provide insight not only of catalytic mechanism, but also suggest a target of structure-based drug design.

Selected figure(s)

Figure 4.
Protein-ligand interaction. The NADP^+ molecule is shown as yellow stick, and the substrate is displayed as green stick. Water molecules are shown as red spheres and metal ions as magenta spheres. Hydrogen bonds are shown as dotted black lines. (A) The interaction between NADP^+ and nucleotide-binding motif GXXXGXG. Of note is that Tyr24, not a basic residue, forms hydrogen bond contact with 2[prime prime or minute]-phosphate group of the adenine ribose. (B) Stereo view of a detailed network of hydrogen bonds formed by Ga5DH and its ligands. The substrate and cofactor are fixed in a plausible position favorable for the subsequent dehydrogenation reaction. The catalytically important residues Tyr163 and Lys167 are shown as cyan stick.

Figure 6.
Proposed reaction mechanism for Ga5DH from S. suis. Note that Ser150 forms a hydrogen bond with the ---OH group at C6 (not C5) of the substrate. The mechanism is described in detail in Discussion.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2009, 18, 294-303) copyright 2009.

Figures were selected by an automated process.