1NH0

1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.03 Å
  • R-Value Free: 0.165 
  • R-Value Work: 0.130 
  • R-Value Observed: 0.131 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation, and Subsite-Pocket Interactions Analyzed at Atomic Resolution

Brynda, J.Rezacova, P.Fabry, M.Horejsi, M.Stouracova, R.Sedlacek, J.Soucek, M.Hradilek, M.Lepsik, M.Konvalinka, J.

(2004) J Med Chem 47: 2030-2036

  • DOI: https://doi.org/10.1021/jm031105q
  • Primary Citation of Related Structures:  
    1NH0

  • PubMed Abstract: 

    The X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses.


  • Organizational Affiliation

    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16637 Prague 6, Czech Republic. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEASE RETROPEPSIN
A, B
99Human immunodeficiency virus 1Mutation(s): 0 
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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
peptidomimetic inhibitor KI2-PHE-GLU-GLU-NH2C [auth I],
D [auth J]
5N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.03 Å
  • R-Value Free: 0.165 
  • R-Value Work: 0.130 
  • R-Value Observed: 0.131 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 28.913α = 90
b = 66.562β = 90
c = 93.147γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
XSCALEdata scaling
EPMRphasing
SHELXL-97refinement
XDSdata reduction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-04-13
    Type: Initial release
  • Version 1.1: 2008-04-29
    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: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description