3NVT

1.95 Angstrom crystal structure of a bifunctional 3-deoxy-7-phosphoheptulonate synthase/chorismate mutase (aroA) from Listeria monocytogenes EGD-e


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.198 
  • R-Value Work: 0.154 
  • R-Value Observed: 0.156 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural analysis of a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with an N-terminal chorismate mutase-like regulatory domain.

Light, S.H.Halavaty, A.S.Minasov, G.Shuvalova, L.Anderson, W.F.

(2012) Protein Sci 21: 887-895

  • DOI: https://doi.org/10.1002/pro.2075
  • Primary Citation of Related Structures:  
    3NVT, 3TFC

  • PubMed Abstract: 

    3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first step in the biosynthesis of a number of aromatic metabolites. Likely because this reaction is situated at a pivotal biosynthetic gateway, several DAHPS classes distinguished by distinct mechanisms of allosteric regulation have independently evolved. One class of DAHPSs contains a regulatory domain with sequence homology to chorismate mutase-an enzyme further downstream of DAHPS that catalyzes the first committed step in tyrosine/phenylalanine biosynthesis-and is inhibited by chorismate mutase substrate (chorismate) and product (prephenate). Described in this work, structures of the Listeria monocytogenes chorismate/prephenate regulated DAHPS in complex with Mn(2+) and Mn(2+) + phosphoenolpyruvate reveal an unusual quaternary architecture: DAHPS domains assemble as a tetramer, from either side of which chorismate mutase-like (CML) regulatory domains asymmetrically emerge to form a pair of dimers. This domain organization suggests that chorismate/prephenate binding promotes a stable interaction between the discrete regulatory and catalytic domains and supports a mechanism of allosteric inhibition similar to tyrosine/phenylalanine control of a related DAHPS class. We argue that the structural similarity of chorismate mutase enzyme and CML regulatory domain provides a unique opportunity for the design of a multitarget antibacterial.


  • Organizational Affiliation

    Center for Structural Genomics of Infectious Diseases, Department of Molecular Pharmacology and Biological Chemistry, 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-deoxy-D-arabino-heptulosonate 7-phosphate synthase
A, B
385Listeria monocytogenes EGD-eMutation(s): 0 
Gene Names: aroAlmo1600
EC: 2.5.1.54 (PDB Primary Data), 5.4.99.5 (PDB Primary Data)
UniProt
Find proteins for Q8Y6T2 (Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e))
Explore Q8Y6T2 
Go to UniProtKB:  Q8Y6T2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8Y6T2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.57α = 90
b = 111.787β = 127.63
c = 81.049γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
HKL-3000data reduction
HKL-3000data scaling

Structure Validation

View Full Validation Report



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: 2012-04-25
    Changes: Database references
  • Version 1.3: 2012-05-30
    Changes: Database references
  • Version 1.4: 2017-11-08
    Changes: Refinement description
  • Version 1.5: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description