9HVP

Design, activity and 2.8 Angstroms crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease.

Erickson, J.Neidhart, D.J.VanDrie, J.Kempf, D.J.Wang, X.C.Norbeck, D.W.Plattner, J.J.Rittenhouse, J.W.Turon, M.Wideburg, N.

(1990) Science 249: 527-533

  • DOI: https://doi.org/10.1126/science.2200122
  • Primary Citation of Related Structures:  
    9HVP

  • PubMed Abstract: 

    A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion.


  • Organizational Affiliation

    Department of Computer-Assisted Molecular Design, Abbott Laboratories, Abbott Park, IL 60064.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 Protease
A, B
99Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: pol
UniProt
Find proteins for P12497 (Human immunodeficiency virus type 1 group M subtype B (isolate NY5))
Explore P12497 
Go to UniProtKB:  P12497
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12497
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0E9
Query on 0E9

Download Ideal Coordinates CCD File 
C [auth A]benzyl [(1R,4S,6S,9R)-4,6-dibenzyl-5-hydroxy-1,9-bis(1-methylethyl)-2,8,11-trioxo-13-phenyl-12-oxa-3,7,10-triazatridec-1-yl]carbamate
C43 H52 N4 O7
GEANBHANAKKWSL-ZQWQDMLBSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0E9 BindingDB:  9HVP Ki: 4.5 (nM) from 1 assay(s)
IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.177 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.3α = 90
b = 63.3β = 90
c = 83.6γ = 120
Software Package:
Software NamePurpose
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1992-04-15
    Type: Initial release
  • Version 1.1: 2008-03-25
    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
  • Version 1.5: 2024-02-14
    Changes: Data collection, Database references, Derived calculations, Source and taxonomy, Structure summary