1MOP

Crystal Structure of a Pantothenate Synthetase from M. tuberculosis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.192 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal Structures of a Pantothenate Synthetase from M. tuberculosis and its Complexes with Substrates and a Reaction Intermediate

Wang, S.Eisenberg, D.

(2003) Protein Sci 12: 1097-1108

  • DOI: https://doi.org/10.1110/ps.0241803
  • Primary Citation of Related Structures:  
    1MOP, 1N2B, 1N2E, 1N2G, 1N2H, 1N2I, 1N2J, 1N2O

  • PubMed Abstract: 

    Pantothenate biosynthesis is essential for the virulence of Mycobacterium tuberculosis, and this pathway thus presents potential drug targets against tuberculosis. We determined the crystal structure of pantothenate synthetase (PS) from M. tuberculosis, and its complexes with AMPCPP, pantoate, and a reaction intermediate, pantoyl adenylate, with resolutions from 1.6 to 2 A. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Its structure reveals a dimer, and each subunit has two domains with tight association between domains. The active-site cavity is on the N-terminal domain, partially covered by the C-terminal domain. One wall of the active site cavity is flexible, which allows the bulky AMPCPP to diffuse into the active site to nearly full occupancy when crystals are soaked in solutions containing AMPCPP. Crystal structures of the complexes with AMPCPP and pantoate indicate that the enzyme binds ATP and pantoate tightly in the active site, and brings the carboxyl oxygen of pantoate near the alpha-phosphorus atom of ATP for an in-line nucleophilic attack. When crystals were soaked with, or grown in the presence of, both ATP and pantoate, a reaction intermediate, pantoyl adenylate, is found in the active site. The flexible wall of the active site cavity becomes ordered when the intermediate is in the active site, thus protecting it from being hydrolyzed. Binding of beta-alanine can occur only after pantoyl adenylate is formed inside the active site cavity. The tight binding of the intermediate pantoyl adenylate suggests that nonreactive analogs of pantoyl adenylate may be inhibitors of the PS enzyme with high affinity and specificity.


  • Organizational Affiliation

    Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics, Molecular Biology Institute, University of California, Los Angeles, 90095-1570, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
pantothenate synthetase
A, B
300Mycobacterium tuberculosisMutation(s): 2 
Gene Names: panC
EC: 6.3.2.1
UniProt
Find proteins for P9WIL5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WIL5 
Go to UniProtKB:  P9WIL5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WIL5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
J [auth B],
K [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
L [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EOH
Query on EOH

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
M [auth B],
N [auth B],
O [auth B]
ETHANOL
C2 H6 O
LFQSCWFLJHTTHZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.192 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.266α = 90
b = 70.929β = 98.69
c = 81.825γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-03-11
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-14
    Changes: Data collection, Refinement description