Inaugural Article: Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase
Abstract
UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the reversible transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein to the glucosamine 3-OH group of UDP-GlcNAc. Escherichia coli LpxA is highly selective for R-3-hydroxymyristate. The crystal structure of the E. coli LpxA homotrimer, determined previously in the absence of lipid substrates or products, revealed that LpxA contains an unusual, left-handed parallel β-helix fold. We have now solved the crystal structures of E. coli LpxA with the bound product UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc at a resolution of 1.74 å and with bound UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc at 1.85 å. The structures of these complexes are consistent with the catalytic mechanism deduced by mutagenesis and with a recent 3.0-å structure of LpxA with bound UDP-GlcNAc. Our structures show how LpxA selects for 14-carbon R-3-hydroxyacyl chains and reveal two modes of UDP binding.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2007
- DOI:
- 10.1073/pnas.0705833104
- Bibcode:
- 2007PNAS..10413543W