1kjf
SUBSTRATE SHAPE DETERMINES SPECIFICITY OF RECOGNITION RECOGNITION FOR HIV-1 PROTEASE: ANALYSIS OF CRYSTAL STRUCTURES OF SIX SUBSTRATE COMPLEXES
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OverviewOverview
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.
About this StructureAbout this Structure
1KJF is a Protein complex structure of sequences from Human immunodeficiency virus 1 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
ReferenceReference
Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes., Prabu-Jeyabalan M, Nalivaika E, Schiffer CA, Structure. 2002 Mar;10(3):369-81. PMID:12005435
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