› 3klh

X-ray diffraction
2.9Å resolution

Crystal structure of AZT-Resistant HIV-1 Reverse Transcriptase crosslinked to post-translocation AZTMP-Terminated DNA (COMPLEX P)

Released:
DOI: 10.2210/pdb3klh/pdb
PDB entry 3klh coloured by chain, front view.
PDB entry 3klh coloured by chain, side view.
PDB entry 3klh coloured by chain, top view.
Source organisms:
Primary publication:
Structural basis of HIV-1 resistance to AZT by excision.
Tu X, Das K, Han Q, Bauman JD, Clark AD, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos SG, Arnold E
Nat Struct Mol Biol 17 1202-9 (2010)
PMID: 20852643

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 hexamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-207785 (preferred)
Entry contents:
4 distinct polypeptide molecules
2 distinct DNA molecules
Macromolecules (6 distinct):
Reverse transcriptase/ribonuclease H Chain: A
Molecule details ›
Chain: A
Length: 564 amino acids
Theoretical weight: 64.99 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli
UniProt:
  • Canonical: P03366 (Residues: 600-1161; 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 type 1 BH10
Expression system: Escherichia coli
UniProt:
  • Canonical: P03366 (Residues: 600-1027; Coverage: 30%)
Gene name: gag-pol
Sequence domains:
Structure domains:
monoclonal antibody, heavy chain Chain: C
Molecule details ›
Chain: C
Length: 211 amino acids
Theoretical weight: 23.36 KDa
Source organism: Mus musculus
Expression system: Not provided
Structure domains: Immunoglobulins
monoclonal antibody, light chain Chain: D
Molecule details ›
Chain: D
Length: 225 amino acids
Theoretical weight: 24 KDa
Source organism: Mus musculus
Expression system: Not provided
Structure domains: Immunoglobulins
DNA (5'-D(*AP*T*GP*CP*TP*AP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3') Chain: E
Molecule details ›
Chain: E
Length: 27 nucleotides
Theoretical weight: 8.37 KDa
DNA (5'-D(*AP*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*(ATM))-3') Chain: F
Molecule details ›
Chain: F
Length: 21 nucleotides
Theoretical weight: 6.49 KDa

Ligands and Environments

1 bound ligand:
Ligand MG 1 x MG
2 modified residues:
Ligand MRG 1 x MRG
Ligand ATM 1 x ATM

Experiments and Validation Details

Entry percentile scores
X-ray source: CHESS BEAMLINE F1
Spacegroup: P3212
Unit cell:
a: 166.472Å b: 166.472Å c: 220.822Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.26 0.26 0.294
Expression systems:
  • Escherichia coli
  • Not provided

Quick links

Citations

19 review citations

Approved Antiviral Drugs over the Past 50 Years.
De Clercq et al. (2016)
18 more

4 mentions without citation

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