3NWY

Structure and allosteric regulation of the uridine monophosphate kinase from Mycobacterium tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.54 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 

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This is version 1.2 of the entry. See complete history


Literature

Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation.

Labesse, G.Benkali, K.Salard-Arnaud, I.Gilles, A.M.Munier-Lehmann, H.

(2011) Nucleic Acids Res 39: 3458-3472

  • DOI: https://doi.org/10.1093/nar/gkq1250
  • Primary Citation of Related Structures:  
    3NWY

  • PubMed Abstract: 

    Nucleoside Monophosphate Kinases (NMPKs) family are key enzymes in nucleotide metabolism. Bacterial UMPKs depart from the main superfamily of NMPKs. Having no eukaryotic counterparts they represent attractive therapeutic targets. They are regulated by GTP and UTP, while showing different mechanisms in Gram(+), Gram(-) and archaeal bacteria. In this work, we have characterized the mycobacterial UMPK (UMPKmt) combining enzymatic and structural investigations with site-directed mutagenesis. UMPKmt exhibits cooperativity toward ATP and an allosteric regulation by GTP and UTP. The crystal structure of the complex of UMPKmt with GTP solved at 2.5 Å, was merely identical to the modelled apo-form, in agreement with SAXS experiments. Only a small stretch of residues was affected upon nucleotide binding, pointing out the role of macromolecular dynamics rather than major structural changes in the allosteric regulation of bacterial UMPKs. We further probe allosteric regulation by site-directed mutagenesis. In particular, a key residue involved in the allosteric regulation of this enzyme was identified.


  • Organizational Affiliation

    Atelier de Bio- et Chimie Informatique Structurale, CNRS, UMR5048, Centre de Biochimie Structurale, 29 rue de Navacelles, F-34090 Montpellier, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Uridylate kinase
A, B, C, D, E
A, B, C, D, E, F
281Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: MT2951MTCY274.14cpyrHRv2883c
EC: 2.7.4.22
UniProt
Find proteins for P9WHK5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WHK5 
Go to UniProtKB:  P9WHK5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WHK5
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.54 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 136.71α = 90
b = 175.48β = 90
c = 65.41γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-08-25
    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