2BB9

Structure of HIV1 protease and AKC4p_133a complex.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.237 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2' side chains

Smith III, A.B.Charnley, A.K.Harada, H.Beiger, J.J.Cantin, L.D.Kenesky, C.S.Hirschmann, R.Munshi, S.Olsen, D.B.Stahlhut, M.W.Schleif, W.A.Kuo, L.C.

(2006) Bioorg Med Chem Lett 16: 859-863

  • DOI: https://doi.org/10.1016/j.bmcl.2005.11.011
  • Primary Citation of Related Structures:  
    2BB9, 2BBB

  • PubMed Abstract: 

    A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally designed P2' side chains have been synthesized and evaluated for activity against wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone inhibitors retain potency in cellular assays against clinically significant mutant forms of the virus. X-ray structures of these inhibitors bound in the wild-type enzyme reveal important insights into the observed biological activity.


  • Organizational Affiliation

    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA. smithhab@sas.upenn.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protease
A, B
99Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: GAG
EC: 3.4.23.16
UniProt
Find proteins for P03367 (Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI))
Explore P03367 
Go to UniProtKB:  P03367
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03367
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
AKC
Query on AKC

Download Ideal Coordinates CCD File 
C [auth A]2-ETHOXYETHYL (1S,2S)-3-{(2S)-4-[(3AS,8S,8AR)-2-OXO-3,3A,8,8A-TETRAHYDRO-2H-INDENO[1,2-D][1,3]OXAZOL-8-YL]-2-BENZYL-3-OXO-2,3-DIHYDRO-1H-PYRROL-2-YL}-1-BENZYL-2-HYDROXYPROPYLCARBAMATE
C36 H39 N3 O7
CGBRFCVAMLJVEA-ZGURCIGKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AKC Binding MOAD:  2BB9 IC50: 0.44 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.237 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.238α = 90
b = 86.18β = 90
c = 46.533γ = 90
Software Package:
Software NamePurpose
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-15
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description