3M7W

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.157 

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Ligand Structure Quality Assessment 


This is version 1.3 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, C, D, E
A, B, C, D, E, F
255Salmonella enterica subsp. enterica serovar Typhimurium str. LT2Mutation(s): 0 
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DQA
Query on DQA

Download Ideal Coordinates CCD File 
G [auth A]
I [auth B]
L [auth C]
Q [auth D]
T [auth E]
G [auth A],
I [auth B],
L [auth C],
Q [auth D],
T [auth E],
X [auth F]
1,3,4-TRIHYDROXY-5-OXO-CYCLOHEXANECARBOXYLIC ACID
C7 H10 O6
WVMWZWGZRAXUBK-SYTVJDICSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A]
J [auth B]
K [auth B]
M [auth C]
N [auth C]
H [auth A],
J [auth B],
K [auth B],
M [auth C],
N [auth C],
O [auth C],
P [auth C],
R [auth D],
S [auth D],
U [auth E],
V [auth E],
W [auth E],
Y [auth F],
Z [auth F]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 184.334α = 90
b = 66.576β = 119.08
c = 128.23γ = 90
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: 2010-04-07
    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: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description