PDBsum entry: 2iz1

Oxidoreductase

PDB id: 2iz1

Contents

Protein chains

470 a.a. *

Ligands

ATR ×3

RES

P33 ×2

PEG

Metals

_CL ×4

Waters ×1899

* Residue conservation analysis

PDB id:

2iz1

Name:

Oxidoreductase

Title:

6pdh complexed with pex inhibitor synchrotron data

Structure:

6-phosphogluconate dehydrogenase, decarboxylating chain: a, b, c. Engineered: yes

Source:

Lactococcus lactis. Organism_taxid: 1358. Strain: mg1363. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.30Å R-factor: 0.140 R-free: 0.198

Authors:

R.Sundaramoorthy,J.Iulek,W.N.Hunter

Key ref:

R.Sundaramoorthy et al. (2007). Crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates. Febs J, 274, 275-286. PubMed id: 17222187 DOI: 10.1111/j.1742-4658.2006.05585.x

Date:

23-Jul-06 Release date: 23-Jan-07

Protein chains

P96789  (6PGD_LACLM) -  6-phosphogluconate dehydrogenase, decarboxylating

Seq: 472 a.a.

Struc: 470 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.1.1.44 - Phosphogluconate dehydrogenase (decarboxylating).
• Pathway: Pentose Phosphate Pathway (early stages)
• Reaction: 6-phospho-D-gluconate + NADP⁺ = D-ribulose 5-phosphate + CO₂ + NADPH

6-phospho-D-gluconate (Bound ligand (Het Group name = RES) matches with 63.16% similarity) + NADP(+) (Bound ligand (Het Group name = ATR) matches with 64.58% similarity) = D-ribulose 5-phosphate + CO(2) + NADPH

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

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation-reduction process (3 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1111/j.1742-4658.2006.05585.x

Febs J 274:275-286 (2007)

PubMed id: 17222187

Crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates.

R.Sundaramoorthy, J.Iulek, M.P.Barrett, O.Bidet, G.F.Ruda, I.H.Gilbert, W.N.Hunter.

ABSTRACT

Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors have been determined. LlPDH shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite Trypanosoma brucei for which structures have been reported. Comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phosphate. However, there are differences in the conformation of the substrate 6-phosphogluconate which may reflect distinct states relevant to catalysis. Analysis of the complex formed with the potent inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does indeed mimic the high-energy intermediate state that it was designed to. The analysis also identified, as a contaminant by-product of the inhibitor synthesis, 4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as a model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species.