1GJ6

ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.

Katz, B.A.Sprengeler, P.A.Luong, C.Verner, E.Elrod, K.Kirtley, M.Janc, J.Spencer, J.R.Breitenbucher, J.G.Hui, H.McGee, D.Allen, D.Martelli, A.Mackman, R.L.

(2001) Chem Biol 8: 1107-1121

  • DOI: https://doi.org/10.1016/s1074-5521(01)00084-9
  • Primary Citation of Related Structures:  
    1GJ4, 1GJ5, 1GJ6, 1GJ7, 1GJ8, 1GJ9, 1GJA, 1GJB, 1GJC, 1GJD

  • PubMed Abstract: 

    Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts.


  • Organizational Affiliation

    Axys Pharmaceutical Corporation, 385 Oyster Point Boulevard, South San Francisco, CA 94080, USA. brad_katz@axyspharm.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-TRYPSIN223Bos taurusMutation(s): 0 
EC: 3.4.21.4
UniProt
Find proteins for P00760 (Bos taurus)
Explore P00760 
Go to UniProtKB:  P00760
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
132
Query on 132

Download Ideal Coordinates CCD File 
C [auth A]6-CHLORO-2-(2-HYDROXY-BIPHENYL-3-YL)-1H-INDOLE-5-CARBOXAMIDINE
C21 H17 Cl N3 O
FEKRWNWZMOSVBX-UHFFFAOYSA-O
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
132 Binding MOAD:  1GJ6 Ki: 230 (nM) from 1 assay(s)
PDBBind:  1GJ6 Ki: 100 (nM) from 1 assay(s)
BindingDB:  1GJ6 Ki: min: 100, max: 230 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.189 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.72α = 90
b = 63.08β = 90
c = 69.5γ = 90
Software Package:
Software NamePurpose
bioteXdata collection
bioteXdata reduction
X-PLORrefinement
bioteXdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-04-27
    Type: Initial release
  • Version 1.1: 2008-04-26
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations