PDBsum entry 3p3c

Hydrolase

PDB id: 3p3c

Contents

Protein chain

272 a.a.

Ligands

3P3

PO4

Metals

_ZN

Waters ×452

PDB id:

3p3c

Name:

Hydrolase

Title:

Crystal structure of the aquifex aeolicus lpxc/lpc-009 complex

Structure:

Udp-3-o-[3-hydroxymyristoyl] n-acetylglucosamine deacetylase. Chain: a. Fragment: unp residues 2-275. Synonym: udp-3-o-acyl-glcnac deacetylase. Engineered: yes. Mutation: yes

Source:

Aquifex aeolicus. Organism_taxid: 63363. Gene: aq_1772, enva, lpxc. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.25Å R-factor: 0.153 R-free: 0.161

Authors:

C.-J.Lee,P.Zhou

Key ref:

C.J.Lee et al. (2011). Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design. Chem Biol, 18, 38-47. PubMed id: 21167751

Date:

04-Oct-10 Release date: 05-Jan-11

Protein chain

O67648  (LPXC_AQUAE) -  UDP-3-O-acyl-N-acetylglucosamine deacetylase from Aquifex aeolicus (strain VF5)

Seq: 282 a.a.

Struc: 272 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.5.1.108 - UDP-3-O-acyl-N-acetylglucosamine deacetylase.
• Reaction: a UDP-3-O-[(3R)-3-hydroxyacyl]-N-acetyl-alpha-D-glucosamine + H2O = a UDP-3-O-[(3R)-3-hydroxyacyl]-alpha-D-glucosamine + acetate
• Cofactor: Zn(2+)

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

Key reference

Chem Biol 18:38-47 (2011)

PubMed id: 21167751

Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design.

C.J.Lee, X.Liang, X.Chen, D.Zeng, S.H.Joo, H.S.Chung, A.W.Barb, S.M.Swanson, R.A.Nicholas, Y.Li, E.J.Toone, C.R.Raetz, P.Zhou.

ABSTRACT

LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections.