1ID5

CRYSTAL STRUCTURE OF BOVINE THROMBIN COMPLEX WITH PROTEASE INHIBITOR ECOTIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions.

Wang, S.X.Esmon, C.T.Fletterick, R.J.

(2001) Biochemistry 40: 10038-10046

  • DOI: https://doi.org/10.1021/bi010712h
  • Primary Citation of Related Structures:  
    1ID5

  • PubMed Abstract: 

    The protease inhibitor ecotin fails to inhibit thrombin despite its broad specificity against serine proteases. A point mutation (M84R) in ecotin results in a 1.5 nM affinity for thrombin, 10(4) times stronger than that of wild-type ecotin. The crystal structure of bovine thrombin is determined in complex with ecotin M84R mutant at 2.5 A resolution. Surface loops surrounding the active site cleft of thrombin have undergone significant structural changes to permit inhibitor binding. Particularly, the insertion loops at residues 60 and 148 in thrombin, which likely mediate the interactions with macromolecules, are displaced when the complex forms. Thrombin and ecotin M84R interact in two distinct surfaces. The loop at residue 99 and the C-terminus of thrombin contact ecotin through mixed polar and nonpolar interactions. The active site of thrombin is filled with eight consecutive amino acids of ecotin and demonstrates thrombin's preference for specific features that are compatible with the thrombin cleavage site: negatively charged-Pro-Val-X-Pro-Arg-hydrophobic-positively charged (P1 Arg is in bold letters). The preference for a Val at P4 is clearly defined. The insertion at residue 60 may further affect substrate binding by moving its adjacent loops that are part of the substrate recognition sites.


  • Organizational Affiliation

    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, California 94143-0446, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THROMBINA [auth L]49Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
Explore P00735 
Go to UniProtKB:  P00735
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00735
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
THROMBINB [auth H]256Bos taurusMutation(s): 0 
EC: 3.4.21.5
UniProt
Find proteins for P00735 (Bos taurus)
Explore P00735 
Go to UniProtKB:  P00735
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00735
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
ECOTINC [auth I]142Escherichia coliMutation(s): 1 
UniProt
Find proteins for P23827 (Escherichia coli (strain K12))
Explore P23827 
Go to UniProtKB:  P23827
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23827
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TRS
Query on TRS

Download Ideal Coordinates CCD File 
E [auth H]2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
CA
Query on CA

Download Ideal Coordinates CCD File 
D [auth H]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.517α = 90
b = 165.377β = 90
c = 83.326γ = 90
Software Package:
Software NamePurpose
MAR345data collection
SCALEPACKdata scaling
X-PLORmodel building
CNSrefinement
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-09-05
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-02-08
    Changes: Structure summary
  • Version 1.4: 2017-02-15
    Changes: Derived calculations
  • Version 1.5: 2017-10-04
    Changes: Refinement description
  • Version 1.6: 2021-10-27
    Changes: Database references, Derived calculations