3DCR

X-ray structure of HIV-1 protease and hydrated form of ketomethylene isostere inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 

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This is version 2.2 of the entry. See complete history


Literature

Crystal structure of chemically synthesized HIV-1 protease and a ketomethylene isostere inhibitor based on the p2/NC cleavage site

Torbeev, V.Y.Mandal, K.Terechko, V.A.Kent, S.B.H.

(2008) Bioorg Med Chem Lett 18: 4554-4557

  • DOI: https://doi.org/10.1016/j.bmcl.2008.07.039
  • Primary Citation of Related Structures:  
    3DCK, 3DCR

  • PubMed Abstract: 

    Here we report the X-ray structures of chemically synthesized HIV-1 protease and the inactive [D25N]HIV-1 protease complexed with the ketomethylene isostere inhibitor Ac-Thr-Ile-Nle psi[CO-CH(2)]Nle-Gln-Arg.amide at 1.4 and 1.8A resolution, respectively. In complex with the active enzyme, the keto-group was found to be converted into the hydrated gem-diol, while the structure of the complex with the inactive D25N enzyme revealed an intact keto-group. These data support the general acid-general base mechanism for HIV-1 protease catalysis.


  • Organizational Affiliation

    Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. torbeev@uchicago.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chemical analogue HIV-1 protease
A, B
99N/AMutation(s): 0 
EC: 3.4.23.16
UniProt
Find proteins for O38732 (Human immunodeficiency virus 1)
Explore O38732 
Go to UniProtKB:  O38732
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO38732
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KVS
Query on KVS

Download Ideal Coordinates CCD File 
C [auth B]N~2~-[(2R,5S)-5-({(2S,3S)-2-[(N-acetyl-L-threonyl)amino]-3-methylpent-4-enoyl}amino)-2-butyl-4,4-dihydroxynonanoyl]-L-glutaminyl-L-argininamide
C36 H68 N10 O10
GHZIZWOGRIROFP-WZGNFWQUSA-N
Modified Residues  3 Unique
IDChains TypeFormula2D DiagramParent
ABA
Query on ABA
A, B
L-PEPTIDE LINKINGC4 H9 N O2ALA
NLE
Query on NLE
A, B
L-PEPTIDE LINKINGC6 H13 N O2LEU
YCM
Query on YCM
A, B
L-PEPTIDE LINKINGC5 H10 N2 O3 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
KVS Binding MOAD:  3DCR IC50: 6.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.2α = 90
b = 58.077β = 90
c = 61.658γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
Locallydata collection
HKL-2000data reduction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-08-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2013-10-16
    Changes: Non-polymer description
  • Version 1.3: 2017-10-25
    Changes: Refinement description
  • Version 2.0: 2019-08-07
    Changes: Data collection, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.2: 2023-11-15
    Changes: Data collection