2VP8

Structure of Mycobacterium tuberculosis Rv1207


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Biochemical and Structural Characterization of the Putative Dihydropteroate Synthase Ortholog Rv1207 of Mycobacterium Tuberculosis.

Gengenbacher, M.Xu, T.Niyomwattanakit, P.Spraggon, G.Dick, T.

(2008) FEMS Microbiol Lett 287: 128

  • DOI: https://doi.org/10.1111/j.1574-6968.2008.01302.x
  • Primary Citation of Related Structures:  
    2VP8

  • PubMed Abstract: 

    Dihydropteroate synthase (DHPS) is involved in de novo biosynthesis of the essential cofactor folate by catalyzing the condensation of para-aminobenzoic acid (pABA) and 6-hydroxymethyl-7,8-dihydropterin-pyrophosphate (H2PtPP). Mycobacterium tuberculosis possesses a functional DHPS (MtDHPS, Rv3608c, folP1) and, based on sequence similarities, a putative ortholog (Rv1207, folP2). Here, we demonstrate that Rv1207 shows a low H2PtPP substrate affinity and lacks enzymatic DHPS activity. However, we found dapsone, a structural analog of pABA and clinically used DHPS inhibitor, to weakly bind both proteins. To gain insights into the lack of DHPS activity of Rv1207, its three-dimensional structure was determined at 2.64 A. The overall fold of both, MtDHPS (1EYE) and Rv1207, is highly conserved and conforms to a classical triosephosphate isomerase barrel arrangement. The predicted H2PtPP-binding pocket of Rv1207 is occupied by a histidine side chain, relative to a leucine residue in MtDHPS, consistent with the low affinity for this substrate and the lack of DHPS activity. We conclude that folP2 does not encode a DHPS and therefore cannot act as bypass for folP1. The metabolic function of Rv1207 remains to be defined.


  • Organizational Affiliation

    Novartis Institute for Tropical Diseases Pte Ltd, Singapore. martin.gengenbacher@novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DIHYDROPTEROATE SYNTHASE 2
A, B
318Mycobacterium tuberculosis H37RvMutation(s): 0 
UniProt
Find proteins for P9WNC9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WNC9 
Go to UniProtKB:  P9WNC9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WNC9
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.727α = 90
b = 80.727β = 90
c = 215.938γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description