› 5j2m

X-ray diffraction
2.43Å resolution

HIV-1 reverse transcriptase in complex with DNA and EFdA-triphosphate, a translocation-defective RT inhibitor

Released:
DOI: 10.2210/pdb5j2m/pdb
PDB entry 5j2m coloured by chain, front view.
PDB entry 5j2m coloured by chain, side view.
PDB entry 5j2m coloured by chain, top view.
Source organism: HIV-1 M:B_HXB2R
Primary publication:
Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA).
Salie ZL, Kirby KA, Michailidis E, Marchand B, Singh K, Rohan LC, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG
Proc Natl Acad Sci U S A 113 9274-9 (2016)
PMID: 27489345

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-118852 (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: 560 amino acids
Theoretical weight: 64.52 KDa
Source organism: HIV-1 M:B_HXB2R
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P04585 (Residues: 588-1147; Coverage: 39%)
Gene name: gag-pol
Sequence domains:
Structure domains:
p51 RT Chain: B
Molecule details ›
Chain: B
Length: 440 amino acids
Theoretical weight: 51.38 KDa
Source organism: HIV-1 M:B_HXB2R
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P04585 (Residues: 588-1027; Coverage: 31%)
Gene name: gag-pol
Sequence domains:
Structure domains:
DNA (5'-D(*AP*CP*AP*GP*TP*CP*CP*CP*TP*GP*TP*TP*CP*GP*GP*(MRG)P*CP*GP*CP*CP*G)-3') Chain: P
Molecule details ›
Chain: P
Length: 21 nucleotides
Theoretical weight: 6.49 KDa
DNA (27-MER) Chain: T
Molecule details ›
Chain: T
Length: 27 nucleotides
Theoretical weight: 8.38 KDa

Ligands and Environments

2 bound ligands:
Ligand MG 3 x MG
Ligand 6FN 1 x 6FN
1 modified residue:
Ligand MRG 1 x MRG

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 4.2.2
Spacegroup: C2221
Unit cell:
a: 167.468Å b: 169.758Å c: 101.951Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.201 0.199 0.233
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

10 review citations

The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold.
Yates et al. (2019)
9 more

10 mentions without citation

4'-Ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591: a novel HIV-1 reverse transcriptase translocation inhibitor.
Markowitz et al. (2018)
9 more