3CUX

Atomic Resolution Structures of Escherichia coli and Bacillis anthracis Malate Synthase A: Comparison with Isoform G and Implications for Structure Based Drug Design


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: comparison with isoform G and implications for structure-based drug discovery

Lohman, J.R.Olson, A.C.Remington, S.J.

(2008) Protein Sci 17: 1935-1945

  • DOI: https://doi.org/10.1110/ps.036269.108
  • Primary Citation of Related Structures:  
    3CUX, 3CUZ, 3CV1, 3CV2

  • PubMed Abstract: 

    Enzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as Mycobacterium tuberculosis and Candida albicans. Two isoforms have been identified for malate synthase, the second enzyme in the pathway. Isoform A, found in fungi and plants, comprises approximately 530 residues, whereas isoform G, found only in bacteria, is larger by approximately 200 residues. Crystal structures of malate synthase isoform G from Escherichia coli and Mycobacterium tuberculosis were previously determined at moderate resolution. Here we describe crystal structures of E. coli malate synthase A (MSA) in the apo form (1.04 A resolution) and in complex with acetyl-coenzyme A and a competitive inhibitor, possibly pyruvate or oxalate (1.40 A resolution). In addition, a crystal structure for Bacillus anthracis MSA at 1.70 A resolution is reported. The increase in size between isoforms A and G can be attributed primarily to an inserted alpha/beta domain that may have regulatory function. Upon binding of inhibitor or substrate, several active site loops in MSA undergo large conformational changes. However, in the substrate bound form, the active sites of isoforms A and G from E. coli are nearly identical. Considering that inhibitors bind with very similar affinities to both isoforms, MSA is as an excellent platform for high-resolution structural studies and drug discovery efforts.


  • Organizational Affiliation

    Department of Physics, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403-1229, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Malate synthase528Bacillus anthracisMutation(s): 0 
Gene Names: aceB
EC: 2.3.3.9
UniProt
Find proteins for A0A6L8PPD0 (Bacillus anthracis)
Explore A0A6L8PPD0 
Go to UniProtKB:  A0A6L8PPD0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A6L8PPD0
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.202 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.865α = 90
b = 52.036β = 98.9
c = 89.107γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-11-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations