Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2002-05-15Keywords
Binding SitesCrystallography, X-Ray
Gene Products, gag
HIV Protease
Humans
Hydrogen Bonding
Ligands
Models, Molecular
Molecular Structure
Peptides
Protein Structure, Secondary
*Protein Structure, Tertiary
Substrate Specificity
Water
Biochemistry, Biophysics, and Structural Biology
Pharmacology, Toxicology and Environmental Health
Metadata
Show full item recordAbstract
The homodimeric HIV-1 protease is the target of some of the most effective antiviral AIDS therapy, as it facilitates viral maturation by cleaving ten asymmetric and nonhomologous sequences in the Gag and Pol polyproteins. Since the specificity of this enzyme is not easily determined from the sequences of these cleavage sites alone, we solved the crystal structures of complexes of an inactive variant (D25N) of HIV-1 protease with six peptides that correspond to the natural substrate cleavage sites. When the protease binds to its substrate and buries nearly 1000 A2 of surface area, the symmetry of the protease is broken, yet most internal hydrogen bonds and waters are conserved. However, no substrate side chain hydrogen bond is conserved. Specificity of HIV-1 protease appears to be determined by an asymmetric shape rather than a particular amino acid sequence.Source
Structure. 2002 Mar;10(3):369-81.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26152PubMed ID
12005435Related Resources
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