› 3tam

X-ray diffraction
2.51Å resolution

Crystal structure of HIV-1 reverse transcriptase (K103N mutant) in complex with inhibitor M06

Released:
DOI: 10.2210/pdb3tam/pdb
PDB entry 3tam coloured by chain, front view.
PDB entry 3tam coloured by chain, side view.
PDB entry 3tam coloured by chain, top view.
Source organism: HIV-1 M:B_HXB2R
Primary publication:
Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase.
Gomez R, Jolly S, Williams T, Tucker T, Tynebor R, Vacca J, McGaughey G, Lai MT, Felock P, Munshi V, DeStefano D, Touch S, Miller M, Yan Y, Sanchez R, Liang Y, Paton B, Wan BL, Anthony N
Bioorg Med Chem Lett 21 7344-50 (2011)
PMID: 22071300

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-138005 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Reverse transcriptase/ribonuclease H Chain: A
Molecule details ›
Chain: A
Length: 563 amino acids
Theoretical weight: 64.88 KDa
Source organism: HIV-1 M:B_HXB2R
Expression system: Escherichia coli
UniProt:
  • Canonical: P04585 (Residues: 590-1147; Coverage: 39%)
Gene name: gag-pol
Sequence domains:
Structure domains:
p51 RT Chain: B
Molecule details ›
Chain: B
Length: 443 amino acids
Theoretical weight: 51.72 KDa
Source organism: HIV-1 M:B_HXB2R
Expression system: Escherichia coli
UniProt:
  • Canonical: P04585 (Residues: 588-1027; Coverage: 31%)
Gene name: gag-pol
Sequence domains:
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand M06 1 x M06
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: C2221
Unit cell:
a: 117.91Å b: 153.9Å c: 155.69Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.196 0.193 0.249
Expression system: Escherichia coli

Quick links

Citations

2 review citations

In search of a treatment for HIV--current therapies and the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Reynolds et al. (2012)
1 more

2 mentions without citation

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