› 6an8

X-ray diffraction
2.6Å resolution

STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE (RT) TERNARY COMPLEX WITH A DOUBLE STRANDED DNA AND AN INCOMING D4TTP AT PH 8.0

Released:
DOI: 10.2210/pdb6an8/pdb
PDB entry 6an8 coloured by chain, front view.
PDB entry 6an8 coloured by chain, side view.
PDB entry 6an8 coloured by chain, top view.
Source organism: Human immunodeficiency virus type 1 BH10
Primary publication:
Structure of HIV-1 reverse transcriptase/d4TTP complex: Novel DNA cross-linking site and pH-dependent conformational changes.
Martinez SE, Bauman JD, Das K, Arnold E
Protein Sci 28 587-597 (2019)
PMID: 30499174

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-119571 (preferred)
Entry contents:
2 distinct polypeptide molecules
2 distinct DNA molecules
Macromolecules (4 distinct):
Reverse transcriptase/ribonuclease H Chains: A, C
Molecule details ›
Chains: A, C
Length: 556 amino acids
Theoretical weight: 64.04 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03366 (Residues: 600-1153; Coverage: 38%)
Gene name: gag-pol
Sequence domains:
p51 RT Chains: B, D
Molecule details ›
Chains: B, D
Length: 444 amino acids
Theoretical weight: 51.93 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:
DNA TEMPLATE (5'- D(*AP*TP*GP*AP*AP*CP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3') Chains: E, T
Molecule details ›
Chains: E, T
Length: 27 nucleotides
Theoretical weight: 8.38 KDa
DNA PRIMER (5'- D(*AP*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*GP*CP*GP*CP*CP*GP)-3') Chains: F, P
Molecule details ›
Chains: F, P
Length: 21 nucleotides
Theoretical weight: 6.4 KDa

Ligands and Environments

3 bound ligands:
Ligand MG 4 x MG
Ligand D4T 2 x D4T
Ligand GOL 13 x GOL
1 modified residue:
Ligand DDG 2 x DDG

Experiments and Validation Details

Entry percentile scores
X-ray source: CHESS BEAMLINE F1
Spacegroup: P21
Unit cell:
a: 89.959Å b: 132.824Å c: 138.909Å
α: 90° β: 97.83° γ: 90°
R-values:
R R work R free
0.178 0.178 0.217
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.
Xavier Ruiz et al. (2020)
5 other articles