› 4eyr

X-ray diffraction
1.8Å resolution

Crystal structure of multidrug-resistant clinical isolate 769 HIV-1 protease in complex with ritonavir

Released:
DOI: 10.2210/pdb4eyr/pdb
PDB entry 4eyr coloured by chain, front view.
PDB entry 4eyr coloured by chain, side view.
PDB entry 4eyr coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
Insights into the mechanism of drug resistance: X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex.
Liu Z, Yedidi RS, Wang Y, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC
Biochem Biophys Res Commun 431 232-8 (2013)
PMID: 23313846

Function and Biology Details

Reaction catalysed: 
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-169395 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Pol protein Chains: A, B
Molecule details ›
Chains: A, B
Length: 99 amino acids
Theoretical weight: 10.77 KDa
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli
UniProt:
  • Canonical: Q000H7 (Residues: 1-99; Coverage: 25%)
Gene name: pol
Sequence domains: Retroviral aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand RIT 1 x RIT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-D
Spacegroup: P41
Unit cell:
a: 45.398Å b: 45.398Å c: 104.071Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.193 0.191 0.226
Expression system: Escherichia coli

Quick links

Citations

4 citation in other articles

Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T↑T Containing 100 Amino Acids Per Monomer.
Lockhat et al. (2016)
3 more

4 mentions without citation

Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease.
Yedidi et al. (2013)
3 more