› 2qi1

X-ray diffraction
2Å resolution

Crystal structure of protease inhibitor, MIT-1-KK81 in complex with wild type HIV-1 protease

Released:
DOI: 10.2210/pdb2qi1/pdb
PDB entry 2qi1 coloured by chain, front view.
PDB entry 2qi1 coloured by chain, side view.
PDB entry 2qi1 coloured by chain, top view.
Source organism: Human immunodeficiency virus 1
Primary publication:
HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants.
Altman MD, Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Chellappan S, Kairys V, Fernandes MX, Gilson MK, Schiffer CA, Rana TM, Tidor B
J Am Chem Soc 130 6099-113 (2008)
PMID: 18412349

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-136879 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Protease Chains: A, B
Molecule details ›
Chains: A, B
Length: 99 amino acids
Theoretical weight: 10.82 KDa
Source organism: Human immunodeficiency virus 1
Expression system: Escherichia coli
UniProt:
  • Canonical: P03369 (Residues: 491-589; Coverage: 7%)
Gene name: gag-pol
Sequence domains: Retroviral aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand PO4 4 x PO4
Ligand MZ4 1 x MZ4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU
Spacegroup: P212121
Unit cell:
a: 50.777Å b: 58.029Å c: 61.779Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.159 0.156 0.205
Expression system: Escherichia coli

Quick links

Citations

8 review citations

Beware of docking!
Chen YC. (2015)
7 more

6 mentions without citation

Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance.
Nalam et al. (2010)
5 more