1HVR

RATIONAL DESIGN OF POTENT, BIOAVAILABLE, NONPEPTIDE CYCLIC UREAS AS HIV PROTEASE INHIBITORS

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history. 


Literature

Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.

Lam, P.Y., Jadhav, P.K., Eyermann, C.J., Hodge, C.N., Ru, Y., Bacheler, L.T., Meek, J.L., Otto, M.J., Rayner, M.M., Wong, Y.N., Chang, C.-H., Weber, P., Jackson, D.A., Sharpe, T.R., Erickson-Viitanen, S.

(1994) Science 263: 380-384

  • DOI: https://doi.org/10.1126/science.8278812
  • Primary Citation of Related Structures:  
    1HVR

  • PubMed Abstract: 

    Mechanistic information and structure-based design methods have been used to design a series of nonpeptide cyclic ureas that are potent inhibitors of human immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen-bonding features of a key structural water molecule. The success of the design in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies. Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized.

    • Organizational Affiliation: 

    Department of Virology Research, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880.


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 
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
XK2
Query on XK2
Download Ideal Coordinates CCD File 
C [auth A][4R-(4ALPHA,5ALPHA,6BETA,7BETA)]-HEXAHYDRO-5,6-DIHYDROXY-1,3-BIS[2-NAPHTHYL-METHYL]-4,7-BIS(PHENYLMETHYL)-2H-1,3-DIAZEPIN-2-ONE
C41 H38 N2 O3
VUYPJDFAKYXJEV-WESAGZJESA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A, B
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
XK2 BindingDB:  1HVR Ki: min: 0.05, max: 0.31 (nM) from 3 assay(s)
Kd: 0.3 (nM) from 1 assay(s)
Binding MOAD:  1HVR Ki: 0.31 (nM) from 1 assay(s)
PDBBind:  1HVR Ki: 0.31 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.8α = 90
b = 62.8β = 90
c = 83.5γ = 120
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 1995-01-26 
    • Deposition Author(s): Chang, C.-H.

Revision History  (Full details and data files)

  • Version 1.0: 1995-01-26
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-02-29
    Changes: Database references
  • Version 1.4: 2017-11-29
    Changes: Derived calculations, Other