2Y85

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS PHOSPHORIBOSYL ISOMERASE WITH BOUND RCDRP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Bisubstrate Specificity in Histidine/Tryptophan Biosynthesis Isomerase from Mycobacterium Tuberculosis by Active Site Metamorphosis.

Due, A.V.Kuper, J.Geerlof, A.Kries, J.P.Wilmanns, M.

(2011) Proc Natl Acad Sci U S A 108: 3554

  • DOI: https://doi.org/10.1073/pnas.1015996108
  • Primary Citation of Related Structures:  
    2Y85, 2Y88, 2Y89

  • PubMed Abstract: 

    In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (β/α)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model. Comparative structural analysis of the active site of the enzyme showed that PriA undergoes a reaction-specific and substrate-induced metamorphosis of the active site architecture, demonstrating its unique ability to essentially form two different substrate-specific actives sites. Furthermore, we found that one of the two catalytic residues in PriA, which are identical in both isomerization reactions, is recruited by a substrate-dependent mechanism into the active site to allow its involvement in catalysis. Comparison of the structural data from PriA with one of the two single-substrate enzymes (TrpF) revealed substantial differences in the active site architecture, suggesting independent evolution. To support these observations, we identified six small molecule compounds that inhibited both PriA-catalyzed isomerization reactions but had no effect on TrpF activity. Our data demonstrate an opportunity for organism-specific inhibition of enzymatic catalysis by taking advantage of the distinct ability for bisubstrate catalysis in the M. tuberculosis enzyme.


  • Organizational Affiliation

    European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, D-22603 Hamburg, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PHOSPHORIBOSYL ISOMERASE A
A, B, C, D
244Mycobacterium tuberculosis H37RvMutation(s): 0 
EC: 5.3.1.24 (PDB Primary Data), 5.3.1.16 (PDB Primary Data)
UniProt
Find proteins for P9WMM5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WMM5 
Go to UniProtKB:  P9WMM5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WMM5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
137
Query on 137

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B],
P [auth C],
U [auth D]
1-(O-CARBOXY-PHENYLAMINO)-1-DEOXY-D-RIBULOSE-5-PHOSPHATE
C12 H18 N O9 P
AULMJMUNCOBRHC-MXWKQRLJSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
F [auth A],
K [auth B],
O [auth C],
T [auth D]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
E [auth A]
H [auth A]
I [auth A]
J [auth B]
M [auth B]
E [auth A],
H [auth A],
I [auth A],
J [auth B],
M [auth B],
N [auth C],
Q [auth C],
R [auth C],
S [auth D],
V [auth D],
W [auth D]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.98α = 90
b = 121.07β = 95.6
c = 81.14γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-03-02
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description