3zsz

X-ray diffraction
2Å resolution

Small molecule inhibitors of the LEDGF site of HIV type 1 integrase identified by fragment screening and structure based drug design

Released:

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

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-146209 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Integrase Chains: A, B
Molecule details ›
Chains: A, B
Length: 167 amino acids
Theoretical weight: 18.4 KDa
Source organism: Human immunodeficiency virus
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P12497 (Residues: 1203-1359; Coverage: 11%)
Gene name: gag-pol
Sequence domains: Integrase core domain
Structure domains: Ribonuclease H-like superfamily/Ribonuclease H

Ligands and Environments

No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX1
Spacegroup: P31
Unit cell:
a: 71.475Å b: 71.475Å c: 66.453Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.188 0.187 0.222
Expression system: Escherichia coli BL21