› 4rw6

X-ray diffraction
2.63Å resolution

Crystal Structure of HIV-1 Reverse Transcriptase (Y181C) variant in complex with (E)-3-(3-chloro-5-(4-chloro-2-(2-(2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)phenyl)acrylonitrile (JLJ494), a Non-nucleoside Inhibitor

Released:
DOI: 10.2210/pdb4rw6/pdb
PDB entry 4rw6 coloured by chain, front view.
PDB entry 4rw6 coloured by chain, side view.
PDB entry 4rw6 coloured by chain, top view.
Source organism: Human immunodeficiency virus type 1 BH10
Primary publication:
Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants.
Frey KM, Puleo DE, Spasov KA, Bollini M, Jorgensen WL, Anderson KS
OpenAccess logo J Med Chem 58 2737-45 (2015)
PMID: 25700160

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: 63.93 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

1 bound ligand:
Ligand 494 1 x 494
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: C2
Unit cell:
a: 161.325Å b: 73.939Å c: 107.601Å
α: 90° β: 99.76° γ: 90°
R-values:
R R work R free
0.236 0.234 0.28
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

6 review citations

Novel diarylpyrimidines and diaryltriazines as potent HIV-1 NNRTIs with dramatically improved solubility: a patent evaluation of US20140378443A1.
Huang et al. (2016)
5 more

2 mentions without citation

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review.
Tarasova et al. (2018)
1 more