1SR9

Crystal Structure of LeuA from Mycobacterium tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis

Koon, N.Squire, C.J.Baker, E.N.

(2004) Proc Natl Acad Sci U S A 101: 8295-8300

  • DOI: https://doi.org/10.1073/pnas.0400820101
  • Primary Citation of Related Structures:  
    1SR9, 3FIG

  • PubMed Abstract: 

    The leucine biosynthetic pathway is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes the first committed step in this pathway, has been determined by multiwavelength anomalous dispersion methods and refined at 2.0-A resolution in complex with its substrate alpha-ketoisovalerate. The structure reveals a tightly associated, domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM barrel catalytic domain, a helical linker domain, and a regulatory domain of novel fold. Mutational and crystallographic data indicate the latter as the site for leucine feedback inhibition of activity. Domain swapping enables the linker domain of one monomer to sit over the catalytic domain of the other, inserting residues into the active site that may be important in catalysis. The alpha-ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity that can accommodate acetyl-CoA. Sequence and structural similarities point to a catalytic mechanism similar to that of malate synthase and an evolutionary relationship with an aldolase that catalyzes the reverse reaction on a similar substrate.


  • Organizational Affiliation

    Centre for Molecular Biodiscovery, School of Biological Sciences, and Department of Chemistry, University of Auckland, Auckland, New Zealand.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2-isopropylmalate synthase
A, B
644Mycobacterium tuberculosisMutation(s): 12 
EC: 2.3.3.13
UniProt
Find proteins for P9WQB3 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WQB3 
Go to UniProtKB:  P9WQB3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WQB3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.25α = 90
b = 154.73β = 98.05
c = 68.82γ = 90
Software Package:
Software NamePurpose
MAR345data collection
SCALEPACKdata scaling
SOLVEphasing
REFMACrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-18
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description