3HSQ

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA.

Robins, L.I.Williams, A.H.Raetz, C.R.

(2009) Biochemistry 48: 6191-6201

  • DOI: https://doi.org/10.1021/bi900629e
  • Primary Citation of Related Structures:  
    3HSQ, 3I3A, 3I3X

  • 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.


  • Organizational Affiliation

    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, North Carolina 27710, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase
A, B, C
259Leptospira interrogansMutation(s): 0 
Gene Names: LA3949LA_3949lpxA
EC: 2.3.1.129
UniProt
Find proteins for Q8EZA6 (Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain 56601))
Explore Q8EZA6 
Go to UniProtKB:  Q8EZA6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8EZA6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 3 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.149α = 90
b = 109.149β = 90
c = 117.124γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Refinement description