› 3jsm

X-ray diffraction
3Å resolution

K65R mutant HIV-1 reverse transcriptase cross-linked to DS-DNA and complexed with tenofovir-diphosphate as the incoming nucleotide substrate

Released:
DOI: 10.2210/pdb3jsm/pdb
PDB entry 3jsm coloured by chain, front view.
PDB entry 3jsm coloured by chain, side view.
PDB entry 3jsm coloured by chain, top view.
Source organism: Human immunodeficiency virus type 1 BH10
Primary publication:
Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance.
Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, Tu X, Clark AD, Boyer PL, Hou X, Gaffney BL, Jones RA, Miller MD, Hughes SH, Arnold E
J Biol Chem 284 35092-100 (2009)
PMID: 19812032

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 tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-116449 (preferred)
Entry contents:
2 distinct polypeptide molecules
2 distinct DNA molecules
Macromolecules (4 distinct):
Reverse transcriptase/ribonuclease H Chain: A
Molecule details ›
Chain: A
Length: 558 amino acids
Theoretical weight: 64.28 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli
UniProt:
  • Canonical: P03366 (Residues: 600-1157; Coverage: 39%)
Gene name: gag-pol
Sequence domains:
Structure domains:
p51 RT Chain: B
Molecule details ›
Chain: B
Length: 437 amino acids
Theoretical weight: 51.1 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli
UniProt:
  • Canonical: P03366 (Residues: 600-1028; Coverage: 30%)
Gene name: gag-pol
Sequence domains:
Structure domains:
DNA (5'-D(*A*TP*GP*GP*TP*CP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3') Chain: T
Molecule details ›
Chain: T
Length: 27 nucleotides
Theoretical weight: 8.38 KDa
DNA (5'-D(*A*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*(DDG))-3') Chain: P
Molecule details ›
Chain: P
Length: 21 nucleotides
Theoretical weight: 6.47 KDa

Ligands and Environments

3 bound ligands:
Ligand TNV 1 x TNV
Ligand MG 2 x MG
Ligand SO4 2 x SO4
2 modified residues:
Ligand MRG 1 x MRG
Ligand DDG 1 x DDG

Experiments and Validation Details

Entry percentile scores
X-ray source: CHESS BEAMLINE F1
Spacegroup: P3112
Unit cell:
a: 170.31Å b: 170.31Å c: 155.44Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.252 0.252 0.285
Expression system: Escherichia coli

Quick links

Citations

13 review citations

HIV-1 reverse transcription.
Hu et al. (2012)
12 more

6 mentions without citation

Avoiding Drug Resistance in HIV Reverse Transcriptase.
Cilento et al. (2021)
5 more