Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase.
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 beta-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 A and with bound UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc at 1.85 A. The structures of these complexes are consistent with the catalytic mechanism deduced by mutagenesis and with a recent 3.0-A 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.
Williams
Allison H
AH
Department of Biochemistry, Duke University Medical Center, Box 3711 DUMC, Durham, NC 27710, USA.
Raetz
Christian R H
CR
D000215:Acylation; D000217:Acyltransferases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007527:Isoenzymes / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry / Q000378:metabolism
D007527:Isoenzymes; D008024:Ligands; D008055:Lipids; D014537:Uridine Diphosphate N-Acetylglucosamine; D000217:Acyltransferases; C050304:acyl-(acyl-carrier-protein)-UDP-N-acetylglucosamine acyltransferase
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