1FV9

Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Work: 0.248 
  • R-Value Observed: 0.248 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Identification of novel inhibitors of urokinase via NMR-based screening.

Hajduk, P.J.Boyd, S.Nettesheim, D.Nienaber, V.Severin, J.Smith, R.Davidson, D.Rockway, T.Fesik, S.W.

(2000) J Med Chem 43: 3862-3866

  • DOI: https://doi.org/10.1021/jm0002228
  • Primary Citation of Related Structures:  
    1FV9

  • PubMed Abstract: 

    Using an NMR-based screen, a novel class of urokinase inhibitors were identified that contain a 2-aminobenzimidazole moiety. The inhibitory potency of this family of inhibitors is similar to that of inhibitors containing a guanidine or amidine group. However, unlike previously described guanidino- or amidino-based inhibitors which have pK(a) values greater than 9.0, urokinase inhibitors containing a 2-aminobenzimidazole have pK(a) values of 7.5. Thus, 2-aminobenzimidazoles may have improved pharmacokinetic properties which could increase the bioavailability of inhibitors which contain this moiety. A crystal structure of one of the lead inhibitors, 2-amino-5-hydroxybenzimidazole, complexed with urokinase reveals the electrostatic and hydrophobic interactions that stabilize complex formation and suggests nearby subsites that may be accessed to increase the potency of this new series of urokinase inhibitors.


  • Organizational Affiliation

    Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UROKINASE245Homo sapiensMutation(s): 0 
EC: 3.4.21.73
UniProt & NIH Common Fund Data Resources
Find proteins for P00749 (Homo sapiens)
Explore P00749 
Go to UniProtKB:  P00749
PHAROS:  P00749
GTEx:  ENSG00000122861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00749
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
172
Query on 172

Download Ideal Coordinates CCD File 
C [auth A]2-AMINO-5-HYDROXY-BENZIMIDAZOLE
C7 H7 N3 O
FNSYWIPPPFVBAV-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
172 PDBBind:  1FV9 IC50: 1.00e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Work: 0.248 
  • R-Value Observed: 0.248 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.16α = 90
b = 53β = 90
c = 82.3γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
AMoREphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2000-10-18 
  • Deposition Author(s): Nienaber, V.

Revision History  (Full details and data files)

  • Version 1.0: 2000-10-18
    Type: Initial release
  • Version 1.1: 2008-04-27
    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: 2018-01-31
    Changes: Experimental preparation