1W66

Structure of a lipoate-protein ligase b from Mycobacterium tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.08 Å
  • R-Value Free: 0.146 
  • R-Value Observed: 0.116 

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This is version 1.5 of the entry. See complete history


Literature

The Mycobacterium Tuberculosis Lipb Enzyme Functions as a Cysteine/Lysine Dyad Acyltransferase.

Ma, Q.Zhao, X.Eddine, A.N.Geerlof, A.Li, X.Cronan, J.E.Kaufmann, S.H.Wilmanns, M.

(2006) Proc Natl Acad Sci U S A 103: 8662

  • DOI: https://doi.org/10.1073/pnas.0510436103
  • Primary Citation of Related Structures:  
    1W66

  • PubMed Abstract: 

    Lipoic acid is essential for the activation of a number of protein complexes involved in key metabolic processes. Growth of Mycobacterium tuberculosis relies on a pathway in which the lipoate attachment group is synthesized from an endogenously produced octanoic acid moiety. In patients with multiple-drug-resistant M. tuberculosis, expression of one gene from this pathway, lipB, encoding for octanoyl-[acyl carrier protein]-protein acyltransferase is considerably up-regulated, thus making it a potential target in the search for novel antiinfectives against tuberculosis. Here we present the crystal structure of the M. tuberculosis LipB protein at atomic resolution, showing an unexpected thioether-linked active-site complex with decanoic acid. We provide evidence that the transferase functions as a cysteine/lysine dyad acyltransferase, in which two invariant residues (Lys-142 and Cys-176) are likely to function as acid/base catalysts. Analysis by MS reveals that the LipB catalytic reaction proceeds by means of an internal thioesteracyl intermediate. Structural comparison of LipB with lipoate protein ligase A indicates that, despite conserved structural and sequence active-site features in the two enzymes, 4'-phosphopantetheine-bound octanoic acid recognition is a specific property of LipB.


  • Organizational Affiliation

    EMBL-Hamburg Unit, European Molecular Biology Laboratory, Notkestrasse 85, 22603 Hamburg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
LIPOYLTRANSFERASE232Mycobacterium tuberculosis H37RvMutation(s): 0 
EC: 2.3.1 (PDB Primary Data), 2.3.1.181 (UniProt)
UniProt
Find proteins for P9WK83 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WK83 
Go to UniProtKB:  P9WK83
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WK83
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DKA
Query on DKA

Download Ideal Coordinates CCD File 
B [auth A]DECANOIC ACID
C10 H20 O2
GHVNFZFCNZKVNT-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.08 Å
  • R-Value Free: 0.146 
  • R-Value Observed: 0.116 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.918α = 90
b = 57.369β = 90
c = 73.804γ = 90
Software Package:
Software NamePurpose
SHELXL-97refinement
DENZOdata reduction
SADABSdata scaling
XPREPphasing
SHELXDphasing
SHELXEphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-12-08
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-03-07
    Changes: Source and taxonomy
  • Version 1.4: 2019-05-22
    Changes: Data collection, Derived calculations, Refinement description
  • Version 1.5: 2019-07-24
    Changes: Data collection