3NNT

Crystal Structure of K170M Mutant of Type I 3-Dehydroquinate Dehydratase (aroD) from Salmonella typhimurium LT2 in Non-Covalent Complex with Dehydroquinate.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 

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This is version 1.4 of the entry. See complete history


Literature

Insights into the mechanism of type I dehydroquinate dehydratases from structures of reaction intermediates.

Light, S.H.Minasov, G.Shuvalova, L.Duban, M.E.Caffrey, M.Anderson, W.F.Lavie, A.

(2011) J Biol Chem 286: 3531-3539

  • DOI: https://doi.org/10.1074/jbc.M110.192831
  • Primary Citation of Related Structures:  
    3JS3, 3M7W, 3NNT

  • PubMed Abstract: 

    The biosynthetic shikimate pathway consists of seven enzymes that catalyze sequential reactions to generate chorismate, a critical branch point in the synthesis of the aromatic amino acids. The third enzyme in the pathway, dehydroquinate dehydratase (DHQD), catalyzes the dehydration of 3-dehydroquinate to 3-dehydroshikimate. We present three crystal structures of the type I DHQD from the intestinal pathogens Clostridium difficile and Salmonella enterica. Structures of the enzyme with substrate and covalent pre- and post-dehydration reaction intermediates provide snapshots of successive steps along the type I DHQD-catalyzed reaction coordinate. These structures reveal that the position of the substrate within the active site does not appreciably change upon Schiff base formation. The intermediate state structures reveal a reaction state-dependent behavior of His-143 in which the residue adopts a conformation proximal to the site of catalytic dehydration only when the leaving group is present. We speculate that His-143 is likely to assume differing catalytic roles in each of its observed conformations. One conformation of His-143 positions the residue for the formation/hydrolysis of the covalent Schiff base intermediates, whereas the other conformation positions the residue for a role in the catalytic dehydration event. The fact that the shikimate pathway is absent from humans makes the enzymes of the pathway potential targets for the development of non-toxic antimicrobials. The structures and mechanistic insight presented here may inform the design of type I DHQD enzyme inhibitors.


  • Organizational Affiliation

    Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-dehydroquinate dehydratase
A, B
276Salmonella enterica subsp. enterica serovar Typhimurium str. LT2Mutation(s): 1 
Gene Names: aroDSTM1358
EC: 4.2.1.10
UniProt
Find proteins for P58687 (Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720))
Explore P58687 
Go to UniProtKB:  P58687
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP58687
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DQA
Query on DQA

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
1,3,4-TRIHYDROXY-5-OXO-CYCLOHEXANECARBOXYLIC ACID
C7 H10 O6
WVMWZWGZRAXUBK-SYTVJDICSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 
  • Space Group: P 1
  • Diffraction Data: https://doi.org/10.18430/M33NNT
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 36.727α = 91.18
b = 43.548β = 101.27
c = 79.938γ = 109.05
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-08
    Changes: Refinement description
  • Version 1.3: 2021-10-06
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description