› 5dgu

X-ray diffraction
1.22Å resolution

Crystal Structure of HIV-1 Protease Inhibitors Containing Substituted fused-Tetrahydropyranyl Tetrahydrofuran as P2-Ligand GRL-004-11A

Released:
DOI: 10.2210/pdb5dgu/pdb
PDB entry 5dgu coloured by chain, front view.
PDB entry 5dgu coloured by chain, side view.
PDB entry 5dgu coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
Design, synthesis, biological evaluation and X-ray structural studies of HIV-1 protease inhibitors containing substituted fused-tetrahydropyranyl tetrahydrofuran as P2-ligands.
Ghosh AK, Martyr CD, Kassekert LA, Nyalapatla PR, Steffey M, Agniswamy J, Wang YF, Weber IT, Amano M, Mitsuya H
Org Biomol Chem 13 11607-21 (2015)
PMID: 26462551

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-138017 (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
UniProt:
  • Canonical: P04585 (Residues: 489-587; Coverage: 7%)
Gene name: gag-pol
Sequence domains: Retroviral aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

4 bound ligands:
Ligand 5B7 1 x 5B7
Ligand NA 2 x NA
Ligand CL 3 x CL
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: 58.642Å b: 86.329Å c: 45.981Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.161 0.159 0.201
Expression system: Escherichia coli

Quick links

Citations

4 citation in other articles

Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20.
Kneller et al. (2019)
3 more

1 mention without citation

Design, synthesis, biological evaluation and X-ray structural studies of HIV-1 protease inhibitors containing substituted fused-tetrahydropyranyl tetrahydrofuran as P2-ligands.
Ghosh et al. (2015)