2VOS

Mycobacterium tuberculosis Folylpolyglutamate synthase complexed with ADP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structures of Mycobacterium Tuberculosisfolylpolyglutamate Synthase Complexed with Adp and Amppcp.

Young, P.G.Smith, C.A.Metcalf, P.Baker, E.N.

(2008) Acta Crystallogr D Biol Crystallogr 64: 745

  • DOI: https://doi.org/10.1107/S0907444908012262
  • Primary Citation of Related Structures:  
    2VOR, 2VOS

  • PubMed Abstract: 

    Folate derivatives are essential vitamins for cell growth and replication, primarily because of their central role in reactions of one-carbon metabolism. Folates require polyglutamation to be efficiently retained within the cell and folate-dependent enzymes have a higher affinity for the polyglutamylated forms of this cofactor. Polyglutamylation is dependent on the enzyme folylpolyglutamate synthetase (FPGS), which catalyzes the sequential addition of several glutamates to folate. FPGS is essential for the growth and survival of important bacterial species, including Mycobacterium tuberculosis, and is a potential drug target. Here, the crystal structures of M. tuberculosis FPGS in complex with ADP and AMPPCP are reported at 2.0 and 2.3 angstroms resolution, respectively. The structures reveal a deeply buried nucleotide-binding site, as in the Escherichia coli and Lactobacillus casei FPGS structures, and a long extended groove for the binding of folate substrates. Differences from the E. coli and L. casei FPGS structures are seen in the binding of a key divalent cation, the carbamylation state of an essential lysine side chain and the adoption of an 'open' position by the active-site beta5-alpha6 loop. These changes point to coordinated events that are associated with dihydropteroate/folate binding and the catalysis of the new amide bond with an incoming glutamate residue.


  • Organizational Affiliation

    School of Biological Sciences, University of Auckland, Auckland, New Zealand. p.young@auckland.ac.nz


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FOLYLPOLYGLUTAMATE SYNTHASE PROTEIN FOLC487Mycobacterium tuberculosis H37RvMutation(s): 0 
EC: 6.3.2.17
UniProt
Find proteins for O53174 (Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh))
Explore O53174 
Go to UniProtKB:  O53174
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO53174
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CO
Query on CO

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A]
COBALT (II) ION
Co
XLJKHNWPARRRJB-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.157 
  • R-Value Observed: 0.158 
  • Space Group: P 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.405α = 90
b = 112.405β = 90
c = 112.405γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
autoSHARPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance