3I3A

Structural Basis for the Sugar Nucleotide and Acyl Chain Selectivity of Leptospira interrogans LpxA

Summary for 3I3A

• Entry DOI: 10.2210/pdb3i3a/pdb
• Related: 3HSQ 3I3X
• Descriptor: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase, S-[2-({N-[(2R)-2-hydroxy-4-{[(S)-hydroxy(methoxy)phosphoryl]oxy}-3,3-dimethylbutanoyl]-beta-alanyl}amino)ethyl] (3R)-3-hydroxydodecanethioate (3 entities in total)
• Functional Keywords: lpxa, leptospira interrogans, leptospira interrogans complex, acyltransferase, lipid a biosynthesis, lipid synthesis, transferase
• Biological source: Leptospira interrogans
• Cellular location: Cytoplasm (By similarity): Q8EZA6
• Total number of polymer chains: 3
• Total formula weight: 86318.29

Authors

Williams, A.H. (deposition date: 2009-06-30, release date: 2009-09-01, Last modification date: 2024-02-21)

Primary citation

Robins, L.I.,Williams, A.H.,Raetz, C.R.
Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA.
Biochemistry, 48:6191-6201, 2009

PubMed Abstract: The first step of lipid A biosynthesis is catalyzed by LpxA in Escherichia coli (EcLpxA), an acyltransferase selective for UDP-GlcNAc and R-3-hydroxymyristoyl-acyl carrier protein (ACP). Leptospira interrogans LpxA (LiLpxA) is extremely selective for R-3-hydroxylauroyl-ACP and an analogue of UDP-GlcNAc, designated UDP-GlcNAc3N, in which NH(2) replaces the GlcNAc 3-OH group. EcLpxA does not discriminate between UDP-GlcNAc and UDP-GlcNAc3N; however, E. coli does not make UDP-GlcNAc3N. With LiLpxA, R-3-hydroxylauroyl-methylphosphopantetheine efficiently substitutes for R-3-hydroxylauroyl-ACP. We now present crystal structures of free LiLpxA and its complexes with its product UDP-3-N-(R-3-hydroxylauroyl)-GlcNAc3N and with its substrate R-3-hydroxylauroyl-methylphosphopantetheine. The positions of the acyl chains of the R-3-hydroxylauroyl-methylphosphopantetheine and the UDP-3-N-(R-3-hydroxylauroyl)-GlcNAc3N are almost identical and are similar to that of the acyl chain in the EcLpxA/UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc complex. The selectivity of LiLpxA for UDP-GlcNAc3N may be explained by the orientation of the backbone carbonyl group of Q68, which differs by approximately 82 degrees from the corresponding Q73 carbonyl group in EcLpxA. This arrangement provides an extra hydrogen-bond acceptor for the 3-NH(2) group of UDP-GlcNAc3N in LiLpxA. The R-3-hydroxylauroyl selectivity of LiLpxA is explained by the position of the K171 side chain, which limits the length of the acyl-chain-binding groove. Our results support the role of LiLpxA H120 (which corresponds to EcLpxA H125) as the catalytic base and provide the first structural information about the orientation of the phosphopantetheine moiety during LpxA catalysis.

PubMed: 19456129
DOI: 10.1021/bi900629e

Experimental method

X-RAY DIFFRACTION (2.12 Å)