› 5vqz

X-ray diffraction
2.23Å resolution

Crystal Structure of HIV-1 Reverse Transcriptase (K103N, Y181C) Variant in Complex with 2-chloro-N-(6-cyano-3-(2-(2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)-4-methylnaphthalen-1-yl)-N-methylacetamide (JLJ686), a Non-nucleoside Inhibitor

Released:
DOI: 10.2210/pdb5vqz/pdb
PDB entry 5vqz coloured by chain, front view.
PDB entry 5vqz coloured by chain, side view.
PDB entry 5vqz coloured by chain, top view.
Source organism: Human immunodeficiency virus type 1 BH10
Primary publication:
Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography.
Chan AH, Lee WG, Spasov KA, Cisneros JA, Kudalkar SN, Petrova ZO, Buckingham AB, Anderson KS, Jorgensen WL
Proc Natl Acad Sci U S A 114 9725-9730 (2017)
PMID: 28827354

Function and Biology Details

Reactions catalysed: 
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
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.
Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-136840 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Reverse transcriptase/ribonuclease H Chain: A
Molecule details ›
Chain: A
Length: 557 amino acids
Theoretical weight: 63.91 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03366 (Residues: 600-1154; Coverage: 38%)
Gene name: gag-pol
Sequence domains:
Structure domains:
p51 RT Chain: B
Molecule details ›
Chain: B
Length: 428 amino acids
Theoretical weight: 50.04 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03366 (Residues: 600-1027; Coverage: 30%)
Gene name: gag-pol
Sequence domains:
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 9HY 1 x 9HY
Ligand SO4 1 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 24-ID-E
Spacegroup: C2
Unit cell:
a: 162.12Å b: 73.33Å c: 108.69Å
α: 90° β: 99.45° γ: 90°
R-values:
R R work R free
0.228 0.227 0.259
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

9 review citations

Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.
Matthew et al. (2021)
8 more

1 mention without citation

Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography.
Chan et al. (2017)