› 1t05

X-ray diffraction
3Å resolution

HIV-1 reverse transcriptase crosslinked to template-primer with tenofovir-diphosphate bound as the incoming nucleotide substrate

Released:
DOI: 10.2210/pdb1t05/pdb
PDB entry 1t05 coloured by chain, front view.
PDB entry 1t05 coloured by chain, side view.
PDB entry 1t05 coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir.
Tuske S, Sarafianos SG, Clark AD, Ding J, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, Wang G, Gaffney BL, Jones RA, Jerina DM, Hughes SH, Arnold E
Nat Struct Mol Biol 11 469-74 (2004)
PMID: 15107837

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 domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-114624 (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: 64.25 KDa
Source organism: Human immunodeficiency virus 1
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: 51.12 KDa
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli
UniProt:
  • Canonical: P04585 (Residues: 588-1018; Coverage: 30%)
Gene name: gag-pol
Sequence domains:
Structure domains:
oligonucleotide template Chain: T
Molecule details ›
Chain: T
Length: 27 nucleotides
Theoretical weight: 8.38 KDa
oligonucleotide primer Chain: P
Molecule details ›
Chain: P
Length: 21 nucleotides
Theoretical weight: 6.47 KDa

Ligands and Environments

3 bound ligands:
Ligand MG 2 x MG
Ligand TNV 1 x TNV
Ligand GOL 5 x GOL
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: 171.57Å b: 171.57Å c: 156.27Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.253 0.253 0.292
Expression system: Escherichia coli

Quick links

Citations

18 review citations

Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.
Csermely et al. (2013)
17 more

27 mentions without citation

Discovery and development of anti-HBV agents and their resistance.
Kim et al. (2010)
26 more