A LEFT-HANDED PARALLEL BETA-HELIX IN THE STRUCTURE OF UDP-N-ACETYLGLUCOSAMINE ACYLTRANSFERASE

UDP-N-acetylglucosamine 3-O-acyltransferase (LpxA) catalyzes the trans fer of (R)-3-hydroxymyristic acid from its acyl carrier protein thioes ter to UDP-N-acetylglucosamine. LpxA is the first enzyme in the lipid A biosynthetic pathway and is a target for the design of antibiotics. The x-ray crystal structure of LpxA has been determined to 2.6 angstro m resolution and reveals a domain motif composed of parallel beta stra nds, termed a left-handed parallel beta helix (L beta H). This unusual fold displays repeated violations of the protein folding constraint r equiring right-handed crossover connections between strands of paralle l beta sheets and may be present in other enzymes that share amino aci d sequence homology to the repeated hexapeptide motif of LpxA.