PDBsum entry 5dg3

Transferase

PDB id: 5dg3

Contents

Protein chains

(+ 0 more) 256 a.a.

Ligands

U21 ×4

PO4

Waters ×231

PDB id:

5dg3

Name:

Transferase

Title:

Structure of pseudomonas aeruginosa lpxa in complex with udp-3-o-(r-3- hydroxydecanoyl)-glcnac

Structure:

Acyl-[acyl-carrier-protein]--udp-n-acetylglucosamine o- acyltransferase. Chain: a, b, c, d, e, f. Synonym: udp-n-acetylglucosamine acyltransferase. Engineered: yes

Source:

Pseudomonas aeruginosa (strain pa7). Organism_taxid: 381754. Strain: pa7. Gene: lpxa, pspa7_1495. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.30Å R-factor: 0.196 R-free: 0.245

Authors:

E.W.Smith,Y.Chen

Key ref:

E.W.Smith et al. (2015). Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity. Biochemistry, 54, 5937-5948. PubMed id: 26352800 DOI: 10.1021/acs.biochem.5b00720

Date:

27-Aug-15 Release date: 16-Sep-15

Protein chains

A6V1E4  (LPXA_PSEA7) -  Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase from Pseudomonas aeruginosa (strain PA7)

Seq: 258 a.a.

Struc: 256 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.129 - acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase.
• Reaction: a (3R)-hydroxyacyl-[ACP] + UDP-N-acetyl-alpha-D-glucosamine = a UDP-3- O-[(3R)-3-hydroxyacyl]-N-acetyl-alpha-D-glucosamine + holo-[ACP]

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

Added reference

DOI no: 10.1021/acs.biochem.5b00720

Biochemistry 54:5937-5948 (2015)

PubMed id: 26352800

Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity.

E.W.Smith, X.Zhang, C.Behzadi, L.D.Andrews, F.Cohen, Y.Chen.

ABSTRACT

In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through the transfer of a R-3-hydroxyacyl chain from the acyl carrier protein (ACP) to the 3-hydroxyl group of UDP-GlcNAc. Previous studies suggest that LpxA is a critical determinant of the acyl chain length found in lipid A, which varies among species of bacteria. In Escherichia coli and Leptospira interrogans, LpxA prefers to incorporate longer R-3-hydroxyacyl chains (C14 and C12, respectively), whereas in Pseudomonas aeruginosa, the enzyme is selective for R-3-hydroxydecanoyl, a 10-hydrocarbon long acyl chain. We now report three P. aeruginosa LpxA crystal structures: apo protein, substrate complex with UDP-GlcNAc, and product complex with UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc. A comparison between the apo form and complexes identifies key residues that position UDP-GlcNAc appropriately for catalysis and supports the role of catalytic His121 in activating the UDP-GlcNAc 3-hydroxyl group for nucleophilic attack during the reaction. The product-complex structure, for the first time, offers structural insights into how Met169 serves to constrain the length of the acyl chain and thus functions as the so-called hydrocarbon ruler. Furthermore, compared with ortholog LpxA structures, the purported oxyanion hole, formed by the backbone amide group of Gly139, displays a different conformation in P. aeruginosa LpxA, which suggests flexibility of this structural feature important for catalysis and the potential need for substrate-induced conformational change in catalysis. Taken together, the three structures provide valuable insights into P. aeruginosa LpxA catalysis and substrate specificity as well as templates for future inhibitor discovery.