PDBsum entry 1pcw

Lyase

PDB id: 1pcw

Contents

Protein chains

257 a.a. *

Ligands

H4P ×2

Metals

_CD ×2

Waters ×340

* Residue conservation analysis

PDB id:

1pcw

Name:

Lyase

Title:

Aquifex aeolicus kdo8ps in complex with cadmium and app, a bisubstrate inhibitor

Structure:

2-dehydro-3-deoxyphosphooctonate aldolase. Chain: a, b. Synonym: phospho-2- dehydro-3-deoxyoctonate aldolase, 3-deoxy-d- manno-octulosonic acid 8-phosphate synthetase, kdo-8-phosphate synthetase, kdo 8-p synthase. Engineered: yes

Source:

Aquifex aeolicus. Organism_taxid: 63363. Gene: kdsa or aq_085. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.85Å R-factor: 0.196 R-free: 0.221

Authors:

X.Xu,J.Wang,C.Grison,S.Petek,P.Coutrot,M.Birck,R.W.Woodard,D.L.Gatti

Key ref:

X.Xu et al. (2003). Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase. Drug Des Discov, 18, 91-99. PubMed id: 14675946

Date:

17-May-03 Release date: 17-Feb-04

Protein chains

O66496  (KDSA_AQUAE) -  2-dehydro-3-deoxyphosphooctonate aldolase from Aquifex aeolicus (strain VF5)

Seq: 267 a.a.

Struc: 257 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.55 - 3-deoxy-8-phosphooctulonate synthase.
• Reaction: D-arabinose 5-phosphate + phosphoenolpyruvate + H2O = 3-deoxy-alpha-D- manno-2-octulosonate-8-phosphate + phosphate

D-arabinose 5-phosphate (Bound ligand (Het Group name = H4P) matches with 66.67% similarity) + phosphoenolpyruvate + H2O = 3-deoxy-alpha-D- manno-2-octulosonate-8-phosphate + phosphate

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

reference

Drug Des Discov 18:91-99 (2003)

PubMed id: 14675946

Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase.

X.Xu, J.Wang, C.Grison, S.Petek, P.Coutrot, M.R.Birck, R.W.Woodard, D.L.Gatti.

ABSTRACT

3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated precursor of KDO, an essential sugar of the lipopolysaccharide of Gram negative bacteria. KDO8P is produced by a specific synthase (KDO8PS) by condensing arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP), with release of inorganic phosphate. As KDO8PS is present in bacteria and plants, but not in mammalian cells, and mutations that inactivate KDO8PS also block cell replication, KDO8PS is a promising target for the design of new antimicrobials that act by blocking lipopolysaccharide biosynthesis. Previous studies have shown that a compound mimicking an intermediate of the condensation reaction is a good ligand and a powerful inhibitor. Here we report on the crystallographic investigation of the binding to KDO8PS of new derivatives of this original inhibitor. The structures of the enzyme in complex with these compounds, and also with the PEP analogs, 2-phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to future strategies for the design of novel inhibitors of KDO8PS.