2IXC

RmlC M. tuberculosis with dTDP-rhamnose


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.79 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.154 

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This is version 1.3 of the entry. See complete history


Literature

Rmlc, a C3' and C5' Carbohydrate Epimerase, Appears to Operate Via an Intermediate with an Unusual Twist Boat Conformation.

Dong, C.Major, L.L.Srikannathasan, V.Errey, J.C.Giraud, M.F.Lam, J.S.Graninger, M.Messner, P.Mcneil, M.R.Field, R.A.Whitfield, C.Naismith, J.H.

(2007) J Mol Biol 365: 146

  • DOI: https://doi.org/10.1016/j.jmb.2006.09.063
  • Primary Citation of Related Structures:  
    2IXC, 2IXH, 2IXI, 2IXJ, 2IXK, 2IXL

  • PubMed Abstract: 

    The striking feature of carbohydrates is their constitutional, conformational and configurational diversity. Biology has harnessed this diversity and manipulates carbohydrate residues in a variety of ways, one of which is epimerization. RmlC catalyzes the epimerization of the C3' and C5' positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. RmlC is the third enzyme of the rhamnose pathway, and represents a validated anti-bacterial drug target. Although several structures of the enzyme have been reported, the mechanism and the nature of the intermediates have remained obscure. Despite its relatively small size (22 kDa), RmlC catalyzes four stereospecific proton transfers and the substrate undergoes a major conformational change during the course of the transformation. Here we report the structure of RmlC from several organisms in complex with product and product mimics. We have probed site-directed mutants by assay and by deuterium exchange. The combination of structural and biochemical data has allowed us to assign key residues and identify the conformation of the carbohydrate during turnover. Clear knowledge of the chemical structure of RmlC reaction intermediates may offer new opportunities for rational drug design.


  • Organizational Affiliation

    Centre for Biomolecular Sciences, The University, St. Andrews KY16 9ST, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC
A, B, C, D
202Mycobacterium tuberculosisMutation(s): 0 
EC: 5.1.3.13
UniProt
Find proteins for P9WH11 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WH11 
Go to UniProtKB:  P9WH11
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WH11
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.79 Å
  • R-Value Free: 0.196 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.154 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.778α = 89.9
b = 56.845β = 78.28
c = 90.7γ = 82.33
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-26
    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: 2019-10-09
    Changes: Data collection, Derived calculations, Experimental preparation, Other