6PRF

HIV-1 Protease multiple drug resistant clinical isolate mutant PR20 with GRL-14213A

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.21 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.154 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20.

Kneller, D.W., Agniswamy, J., Ghosh, A.K., Weber, I.T.

(2019) Biochem Biophys Res Commun 519: 61-66

  • DOI: https://doi.org/10.1016/j.bbrc.2019.08.126
  • Primary Citation of Related Structures:  
    6PRF

  • PubMed Abstract: 

    Drug-resistance threatens effective treatment of HIV/AIDS. Clinical inhibitors, including darunavir (1), are ineffective for highly resistant protease mutant PR20, however, antiviral compound 2 derived from 1 with fused tricyclic group at P2, extended amino-benzothiazole P2' ligand and two fluorine atoms on P1 shows 16-fold better inhibition of PR20 enzyme activity. Crystal structures of PR20 and wild-type PR complexes reveal how the extra groups of 2 counteract the expanded ligand-binding pocket, dynamic flaps, and faster dimer dissociation of PR20.

    • Organizational Affiliation: 

    Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protease
A, B
99Human immunodeficiency virus type 1 BH10Mutation(s): 22 
Gene Names: gag-pol
EC: 3.4.23.16
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7OA (Subject of Investigation/LOI)
Query on 7OA
Download Ideal Coordinates CCD File 
G [auth B](3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl [(2S,3R)-4-[{[2-(cyclopropylamino)-1,3-benzothiazol-6-yl]sulfonyl}(2-methylpropyl)amino]-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]carbamate
C33 H40 F2 N4 O7 S2
ARWGTMGGJGADTI-VFGYXJDYSA-N
Y1
Query on Y1
Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
H [auth B]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
H [auth B],
I [auth B],
J [auth B],
K [auth B],
L [auth B]
YTTRIUM ION
Y
KAJPZYFHSCFBCI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
7OA Binding MOAD:  6PRF Ki: 2.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.21 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.154 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.565α = 90
b = 60.565β = 90
c = 85.139γ = 120
Software Package:
Software NamePurpose
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesAI150461

Revision History  (Full details and data files)

  • Version 1.0: 2019-09-18
    Type: Initial release
  • Version 1.1: 2019-10-09
    Changes: Data collection, Database references
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description