2PUL

Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.205 

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Ligand Structure Quality Assessment 


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Literature

Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding

Ku, S.-Y.Yip, P.Cornell, K.A.Riscoe, M.K.Behr, J.-B.Guillerm, G.Howell, P.L.

(2007) J Biol Chem 282: 22195-22206

  • DOI: https://doi.org/10.1074/jbc.M611045200
  • Primary Citation of Related Structures:  
    2PU8, 2PUI, 2PUL, 2PUN, 2PUP

  • PubMed Abstract: 

    The methionine salvage pathway is ubiquitous in all organisms, but metabolic variations exist between bacteria and mammals. 5-Methylthioribose (MTR) kinase is a key enzyme in methionine salvage in bacteria and the absence of a mammalian homolog suggests that it is a good target for the design of novel antibiotics. The structures of the apo-form of Bacillus subtilis MTR kinase, as well as its ADP, ADP-PO(4), AMPPCP, and AMPPCP-MTR complexes have been determined. MTR kinase has a bilobal eukaryotic protein kinase fold but exhibits a number of unique features. The protein lacks the DFG motif typically found at the beginning of the activation loop and instead coordinates magnesium via a DXE motif (Asp(250)-Glu(252)). In addition, the glycine-rich loop of the protein, analogous to the "Gly triad" in protein kinases, does not interact extensively with the nucleotide. The MTR substrate-binding site consists of Asp(233) of the catalytic HGD motif, a novel twin arginine motif (Arg(340)/Arg(341)), and a semi-conserved W-loop, which appears to regulate MTR binding specificity. No lobe closure is observed for MTR kinase upon substrate binding. This is probably because the enzyme lacks the lobe closure/inducing interactions between the C-lobe of the protein and the ribosyl moiety of the nucleotide that are typically responsible for lobe closure in protein kinases. The current structures suggest that MTR kinase has a dissociative mechanism.


  • Organizational Affiliation

    Program in Molecular Structure and Function, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Methylthioribose kinase
A, B
397Bacillus subtilisMutation(s): 0 
Gene Names: mtnKykrT
EC: 2.7.1.100
UniProt
Find proteins for O31663 (Bacillus subtilis (strain 168))
Explore O31663 
Go to UniProtKB:  O31663
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO31663
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 214.15α = 90
b = 83.47β = 90
c = 51.26γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata scaling
d*TREKdata reduction
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2007-05-22 
  • Deposition Author(s): Ku, S.-Y.

Revision History  (Full details and data files)

  • Version 1.0: 2007-05-22
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations, Refinement description