5ER2

High-resolution X-ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor. the analysis of the inhibitor binding and description of the rigid body shift in the enzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.160 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

High-resolution X-ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor: the analysis of the inhibitor binding and description of the rigid body shift in the enzyme.

Sali, A.Veerapandian, B.Cooper, J.B.Foundling, S.I.Hoover, D.J.Blundell, T.L.

(1989) EMBO J 8: 2179-2188

  • DOI: https://doi.org/10.1002/j.1460-2075.1989.tb08340.x
  • Primary Citation of Related Structures:  
    5ER2

  • PubMed Abstract: 

    The conformation of the synthetic renin inhibitor CP-69,799, bound to the active site of the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6), has been determined by X-ray diffraction at 1.8 A resolution and refined to the crystallographic R factor of 16%. CP-69,799 is an oligopeptide transition--state analogue inhibitor that contains a new dipeptide isostere at the P1-P1' position. This dipeptide isostere is a nitrogen analogue of the well-explored hydroxyethylene dipeptide isostere, wherein the tetrahedral P1' C alpha atom has been replaced by trigonal nitrogen. The inhibitor binds in the extended conformation, filling S4 to S3' pockets, with hydroxyl group of the P1 residue positioned symmetrically between the two catalytic aspartates of the enzyme. Interactions between the inhibitor and the enzyme include 12 hydrogen bonds and extensive van der Waals contacts in all the pockets, except for S3'. The crystal structure reveals a bifurcated orientation of the P2 histidine side chain and an interesting relative rotation of the P3 phenyl ring to accommodate the cyclohexyl side chain at P1. The binding of the inhibitor to the enzyme, while producing no large distortions in the enzyme active site cleft, results in small but significant change in the relative orientation of the two endothiapepsin domains. This structural change may represent the action effected by the proteinase as it distorts its substrate towards the transition state for proteolytic cleavage.


  • Organizational Affiliation

    Department of Crystallography, Birkbeck College, University of London, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ENDOTHIAPEPSINA [auth E]330Cryphonectria parasiticaMutation(s): 0 
EC: 3.4.23.6
UniProt
Find proteins for P11838 (Cryphonectria parasitica)
Explore P11838 
Go to UniProtKB:  P11838
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11838
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0EK
Query on 0EK

Download Ideal Coordinates CCD File 
B [auth E]6-ammonio-N-{[(2R,3R)-3-{[N-(tert-butoxycarbonyl)-L-phenylalanyl-3-(1H-imidazol-3-ium-4-yl)-L-alanyl]amino}-4-cyclohexyl-2-hydroxybutyl](2-methylpropyl)carbamoyl}-L-norleucyl-L-phenylalanine
C50 H77 N9 O9
QBCYEBFUOBJJAC-KHVQSSSXSA-P
Binding Affinity Annotations 
IDSourceBinding Affinity
0EK Binding MOAD:  5ER2 Ki: 270 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.160 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.9α = 90
b = 75.8β = 96.9
c = 42.9γ = 90
Software Package:
Software NamePurpose
PROLSQrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1991-04-15
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other
  • Version 1.4: 2017-11-29
    Changes: Derived calculations, Other