› 7to6

X-ray diffraction
1.21Å resolution

HIV-1 wild type protease with GRL-01717A, with C-4 substituted cyclohexane-fused bis-tetrahydrofuran (Chf-THF) derivatives as P2-ligand [diastereomer 2]

Released:
DOI: 10.2210/pdb7to6/pdb
PDB entry 7to6 coloured by chain, front view.
PDB entry 7to6 coloured by chain, side view.
PDB entry 7to6 coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
Design, Synthesis and X-Ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing C-4 Substituted Tricyclic Hexahydro-Furofuran Derivatives as P2 Ligands.
Ghosh AK, Kovela S, Sharma A, Shahabi D, Ghosh AK, Hopkins DR, Yadav M, Johnson ME, Agniswamy J, Wang YF, Hattori SI, Higashi-Kuwata N, Aoki M, Amano M, Weber IT, Mitsuya H
ChemMedChem 17 e202200058 (2022)
PMID: 35170223

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:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-527557 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Protease Chains: A, B
Molecule details ›
Chains: A, B
Length: 99 amino acids
Theoretical weight: 10.74 KDa
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03367 (Residues: 501-599; Coverage: 7%)
Gene name: gag-pol
Sequence domains: Retroviral aspartyl protease

Ligands and Environments

4 bound ligands:
Ligand NA 1 x NA
Ligand CL 3 x CL
Ligand G77 1 x G77
Ligand ACT 1 x ACT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-BM
Spacegroup: P21212
Unit cell:
a: 58.732Å b: 86.238Å c: 45.961Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.159 0.157 0.188
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 mention without citation

Design, Synthesis and X-Ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing C-4 Substituted Tricyclic Hexahydro-Furofuran Derivatives as P2 Ligands.
Ghosh et al. (2022)