Retroviral proteases.
The proteases of retroviruses, such as leukemia viruses, immunodeficiency viruses (including the human immunodeficiency virus, HIV), infectious anemia viruses, and mammary tumor viruses, form a family with the proteases encoded by several retrotransposons in Drosophila and yeast and endogenous viral sequences in primates. Retroviral proteases are key enzymes in viral propagation and are initially synthesized with other viral proteins as polyprotein precursors that are subsequently cleaved by the viral protease activity at specific sites to produce mature, functional units. Active retroviral proteases are homodimers, with each dimer structurally related to the larger class of single-chain aspartic peptidases. Each monomer has four structural elements: two distinct hairpin loops, a wide loop containing the catalytic aspartic acid and an alpha helix. Retroviral gene sequences can vary between infected individuals, and mutations affecting the binding cleft of the protease or the substrate cleavage sites can alter the response of the virus to therapeutic drugs. The need to develop new drugs against HIV will continue to be, to a large extent, the driving force behind further characterization of retroviral proteases.
Dunn
Ben M
BM
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA. bdunn@college.med.ufl.edu
Goodenow
Maureen M
MM
Gustchina
Alla
A
Wlodawer
Alexander
A
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D001665:Binding Sites; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D019143:Evolution, Molecular; D005814:Genes, Viral; D016333:HIV Protease / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D012190:Retroviridae / Q000201:enzymology* / Q000235:genetics; D012191:Retroviridae Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
D012191:Retroviridae Proteins; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease