› 3qlh

X-ray diffraction
2.7Å resolution

HIV-1 Reverse Transcriptase in Complex with Manicol at the RNase H Active Site and TMC278 (Rilpivirine) at the NNRTI Binding Pocket

Released:
DOI: 10.2210/pdb3qlh/pdb
PDB entry 3qlh coloured by chain, front view.
PDB entry 3qlh coloured by chain, side view.
PDB entry 3qlh coloured by chain, top view.
Source organism: Human immunodeficiency virus type 1 BH10
Primary publication:
Synthesis, activity, and structural analysis of novel α-hydroxytropolone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H.
Chung S, Himmel DM, Jiang JK, Wojtak K, Bauman JD, Rausch JW, Wilson JA, Beutler JA, Thomas CJ, Arnold E, Le Grice SF
J Med Chem 54 4462-73 (2011)
PMID: 21568335

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-136840 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Reverse transcriptase/ribonuclease H Chain: A
Molecule details ›
Chain: A
Length: 555 amino acids
Theoretical weight: 63.8 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P03366 (Residues: 600-1153; Coverage: 38%)
Gene name: gag-pol
Sequence domains:
Structure domains:
p51 RT Chain: B
Molecule details ›
Chain: B
Length: 423 amino acids
Theoretical weight: 49.53 KDa
Source organism: Human immunodeficiency virus type 1 BH10
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P03366 (Residues: 605-1027; Coverage: 29%)
Gene name: gag-pol
Sequence domains:
Structure domains:

Ligands and Environments

5 bound ligands:
Ligand MNK 1 x MNK
Ligand T27 1 x T27
Ligand MN 2 x MN
Ligand DMS 1 x DMS
Ligand EDO 1 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: C2
Unit cell:
a: 163.926Å b: 72.978Å c: 108.377Å
α: 90° β: 101.11° γ: 90°
R-values:
R R work R free
0.232 0.231 0.251
Expression system: Escherichia coli BL21

Quick links

Citations

7 review citations

Human immunodeficiency virus reverse transcriptase: 25 years of research, drug discovery, and promise.
Le Grice SF. (2012)
6 more

5 mentions without citation

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