1C9D

CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXY-4-FLUOROPHENYLTHIO)-BUTYLPHOSPHONIC ACID


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase.

Sachpatzidis, A.Dealwis, C.Lubetsky, J.B.Liang, P.H.Anderson, K.S.Lolis, E.

(1999) Biochemistry 38: 12665-12674

  • DOI: https://doi.org/10.1021/bi9907734
  • Primary Citation of Related Structures:  
    1C29, 1C8V, 1C9D, 1CW2, 1CX9

  • PubMed Abstract: 

    In an effort to use a structure-based approach for the design of new herbicides, the crystal structures of complexes of tryptophan synthase with a series of phosphonate enzyme inhibitors were determined at 2.3 A or higher resolution. These inhibitors were designed to mimic the transition state formed during the alpha-reaction of the enzyme and, as expected, have affinities much greater than that of the natural substrate indole-3-glycerol phosphate or its nonhydrolyzable analogue indole propanol phosphate (IPP). These inhibitors are ortho-substituted arylthioalkylphosphonate derivatives that have an sp(3)-hybridized sulfur atom, designed to mimic the putative tetrahedral transition state at the C3 atom of the indole, and lack the C2 atom to allow for higher conformational flexibility. Overall, the inhibitors bind in a fashion similar to that of IPP. Glu-49 and Phe-212 are the two active site residues whose conformation changes upon inhibitor binding. A very short hydrogen bond between a phosphonate oxygen and the Ser-235 hydroxyl oxygen may be responsible for stabilization of the enzyme-inhibitor complexes. Implications for the mechanism of catalysis as well as directions for more potent inhibitors are discussed.


  • Organizational Affiliation

    Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRYPTOPHAN SYNTHASE (ALPHA CHAIN)268Salmonella enterica subsp. enterica serovar TyphimuriumMutation(s): 0 
EC: 4.2.1.20
UniProt
Find proteins for P00929 (Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720))
Explore P00929 
Go to UniProtKB:  P00929
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00929
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
TRYPTOPHAN SYNTHASE (BETA CHAIN)397Salmonella enterica subsp. enterica serovar TyphimuriumMutation(s): 0 
EC: 4.2.1.20
UniProt
Find proteins for P0A2K1 (Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720))
Explore P0A2K1 
Go to UniProtKB:  P0A2K1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A2K1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HF1
Query on HF1

Download Ideal Coordinates CCD File 
C [auth A]4-(2-HYDROXY-4-FLUOROPHENYLTHIO)-BUTYLPHOSPHONIC ACID
C10 H12 F O4 P S
UXOYJQMPYTYCMG-ORCRQEGFSA-N
PLP
Query on PLP

Download Ideal Coordinates CCD File 
E [auth B]PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
D [auth B]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HF1 PDBBind:  1C9D IC50: 499 (nM) from 1 assay(s)
Binding MOAD:  1C9D IC50: 499 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.215 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 184.22α = 90
b = 60.52β = 94.43
c = 67.79γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
CCP4data scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-12-29
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references, Derived calculations, Source and taxonomy, Structure summary