3hsq

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

Structural highlights

3hsq is a 3 chain structure with sequence from Leptospira interrogans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8EZA6_LEPIN Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[SAAS:SAAS00064151]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA.,Robins LI, Williams AH, Raetz CR Biochemistry. 2009 Jul 7;48(26):6191-201. PMID:19456129^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Robins LI, Williams AH, Raetz CR. Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA. Biochemistry. 2009 Jul 7;48(26):6191-201. PMID:19456129 doi:10.1021/bi900629e