1EPO

ENDOTHIA ASPARTIC PROTEINASE (ENDOTHIAPEPSIN) COMPLEXED WITH CP-81,282 (MOR PHE NLE CHF NME)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Direct observation by X-ray analysis of the tetrahedral intermediate of aspartic proteinases.

Veerapandian, B.Cooper, J.B.Sali, A.Blundell, T.L.Rosati, R.L.Dominy, B.W.Damon, D.B.Hoover, D.J.

(1992) Protein Sci 1: 322-328

  • DOI: https://doi.org/10.1002/pro.5560010303
  • Primary Citation of Related Structures:  
    1EPO

  • PubMed Abstract: 

    We report the X-ray analysis at 2.0 A resolution for crystals of the aspartic proteinase endothiapepsin (EC 3.4.23.6) complexed with a potent difluorostatone-containing tripeptide renin inhibitor (CP-81,282). The scissile bond surrogate, an electrophilic ketone, is hydrated in the complex. The pro-(R) (statine-like) hydroxyl of the tetrahedral carbonyl hydrate is hydrogen-bonded to both active-site aspartates 32 and 215 in the position occupied by a water in the native enzyme. The second hydroxyl oxygen of the hydrate is hydrogen-bonded only to the outer oxygen of Asp 32. These experimental data provide a basis for a model of the tetrahedral intermediate in aspartic proteinase-mediated cleavage of the amide bond. This indicates a mechanism in which Asp 32 is the proton donor and Asp 215 carboxylate polarizes a bound water for nucleophilic attack. The mechanism involves a carboxylate (Asp 32) that is stabilized by extensive hydrogen bonding, rather than an oxyanion derivative of the peptide as in serine proteinase catalysis.


  • Organizational Affiliation

    Department of Crystallography, Birkbeck College, 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: 3.4.23.22
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
2Z3
Query on 2Z3

Download Ideal Coordinates CCD File 
B [auth E]N-(morpholin-4-ylcarbonyl)-L-phenylalanyl-N-[(1R)-1-(cyclohexylmethyl)-3,3-difluoro-2,2-dihydroxy-4-(methylamino)-4-oxobutyl]-L-norleucinamide
C32 H49 F2 N5 O7
IPZOKQNUWWOCTK-GSDHBNRESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
2Z3 Binding MOAD:  1EPO Ki: 11 (nM) from 1 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 2
IDChains NameType/Class2D Diagram3D Interactions
PRD_000416 (2Z3)
Query on PRD_000416
B [auth E]CP-81,282, MOR-PHE-NLE-CHF-NMEPeptide-like / Inhibitor
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Observed: 0.180 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.7α = 90
b = 73.9β = 110
c = 45.8γ = 90
Software Package:
Software NamePurpose
RESTRAINrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-12-20
    Type: Initial release
  • Version 1.1: 2008-03-10
    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