1GNO

HIV-1 PROTEASE (WILD TYPE) COMPLEXED WITH U89360E (INHIBITOR)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Work: 0.174 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases.

Hong, L.Treharne, A.Hartsuck, J.A.Foundling, S.Tang, J.

(1996) Biochemistry 35: 10627-10633

  • DOI: https://doi.org/10.1021/bi960481s
  • Primary Citation of Related Structures:  
    1GNM, 1GNN, 1GNO

  • PubMed Abstract: 

    Crystal structures of the protease of human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D and V82N, have been determined. In all three cases the enzyme forms a complex with the peptidic inhibitor U-89360E. All structures have been determined to 2.3 A resolution and have satisfactory agreement factors: 0.173 for wild type, 0.175 for V82D, and 0.182 for V82N. Comparison of the three crystal structures provides explanations which are consistent with the known kinetic properties of these mutant enzymes with the U-89360E inhibitor [Lin, Y., Lin, X., Hong, L., Foundling, S., Heinrikson, R. L., Thaisrivongs, S., Leelamanit, W., Raterman, D., Shah, M., Dunn, B.M., & Tang, J. (1995) Biochemistry 34, 1143-1152]. Unfavorable van der Waals interactions between the inhibitor and the mutated side chains at position 82 are consistent with diminished affinity for the inhibitor by the mutant enzymes. If a mutation is potentially resistant to an inhibitor, the mutant enzyme should not only have an increased Ki for the inhibitor but should also preserve considerable catalytic capability. The V82D mutant possesses these qualities. In the V82D crystal structure, a water molecule, which connects the protease flap to the inhibitor, is missing or of low occupancy. Absence of this bridge may be important in determining catalytic capability. Moreover, mutation at position 82 induces change in two polypeptide backbone regions, 35-41 and 67-68, which may be related to protease flap mobility.


  • Organizational Affiliation

    Protein Studies Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.


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 
EC: 2.7.7.49
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
U0E
Query on U0E

Download Ideal Coordinates CCD File 
C [auth B],
D [auth B]
N-[[1-[N-ACETAMIDYL]-[1-CYCLOHEXYLMETHYL-2-HYDROXY-4-ISOPROPYL]-BUT-4-YL]-CARBONYL]-GLUTAMINYL-ARGINYL-AMIDE
C28 H52 N8 O6
XTOQWMLQBSGKOK-VUBDRERZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
U0E Binding MOAD:  1GNO Ki: 20 (nM) from 1 assay(s)
PDBBind:  1GNO Ki: 20 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Work: 0.174 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.16α = 90
b = 63.16β = 90
c = 83.59γ = 120
Software Package:
Software NamePurpose
CCP4model building
PROLSQrefinement
SAINTdata reduction
SAINTdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1996-11-08
    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: 2024-02-07
    Changes: Data collection, Database references, Derived calculations, Other