3MRS

Crystal structure of shikimate kinase mutant (R57A) from Helicobacter pylori


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.246 
  • R-Value Observed: 0.247 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structures of Helicobacter pylori shikimate kinase reveal a selective inhibitor-induced-fit mechanism

Cheng, W.C.Chen, Y.F.Wang, H.J.Hsu, K.C.Lin, S.C.Chen, T.J.Yang, J.M.Wang, W.C.

(2012) PLoS One 7: e33481-e33481

  • DOI: https://doi.org/10.1371/journal.pone.0033481
  • Primary Citation of Related Structures:  
    3HR7, 3MRS, 3MUF, 3N2E

  • PubMed Abstract: 

    Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive target pathway for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here we investigated the detailed structure-activity relationship of SK from Helicobacter pylori (HpSK). Site-directed mutagenesis and isothermal titration calorimetry studies revealed critical conserved residues (D33, F48, R57, R116, and R132) that interact with shikimate and are therefore involved in catalysis. Crystal structures of HpSK·SO(4), R57A, and HpSK•shikimate-3-phosphate • ADP show a characteristic three-layer architecture and a conformationally elastic region consisting of F48, R57, R116, and R132, occupied by shikimate. The structure of the inhibitor complex, E114A • 162535, was also determined, which revealed a dramatic shift in the elastic LID region and resulted in conformational locking into a distinctive form. These results reveal considerable insight into the active-site chemistry of SKs and a selective inhibitor-induced-fit mechanism.


  • Organizational Affiliation

    Institute of Molecular and Cellular Biology and Department of Life Sciences, National Tsing Hua University, Hsinchu, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Shikimate kinase168Helicobacter pylori 26695Mutation(s): 1 
Gene Names: AROK
EC: 2.7.1.71
UniProt
Find proteins for P56073 (Helicobacter pylori (strain ATCC 700392 / 26695))
Explore P56073 
Go to UniProtKB:  P56073
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56073
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.246 
  • R-Value Observed: 0.247 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.899α = 90
b = 88.899β = 90
c = 39.874γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-05-30
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Refinement description