› 4fl8

X-ray diffraction
1.2Å resolution

HIV-1 protease complexed with gem-diol-amine tetrahedral intermediate

Released:
DOI: 10.2210/pdb4fl8/pdb
PDB entry 4fl8 coloured by chain, front view.
PDB entry 4fl8 coloured by chain, side view.
PDB entry 4fl8 coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease.
Shen CH, Tie Y, Yu X, Wang YF, Kovalevsky AY, Harrison RW, Weber IT
Biochemistry 51 7726-32 (2012)
PMID: 22963370

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-136856 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
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
Structure domains: Acid Proteases
Protease Chain: C
Molecule details ›
Chain: C
Length: 7 amino acids
Theoretical weight: 801 Da
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03367 (Residues: 561-566; Coverage: 0%)
Gene name: gag-pol
Protease Chain: D
Molecule details ›
Chain: D
Length: 7 amino acids
Theoretical weight: 895 Da
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P03367 (Residues: 559-565; Coverage: 1%)
Gene name: gag-pol

Ligands and Environments

2 bound ligands:
Ligand CL 5 x CL
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-ID
Spacegroup: P21212
Unit cell:
a: 58.405Å b: 86.199Å c: 46.357Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.144 0.142 0.176
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

1 review citation

Transition States, analogues, and drug development.
Schramm VL. (2013)
5 other articles

2 mentions without citation

Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease.
Shen et al. (2012)
1 more