Activity of linked HIV-1 proteinase dimers containing mutations in the active site region.
Mutations were introduced into the active site triplet (Asp-Thr-Gly) of one or both subunits of a linked dimer of human immunodeficiency virus type 1 proteinase. Mutation of Thr to Ser in one or both subunits did not alter the activity of the enzyme substantially, whereas its mutation to Asn in one subunit caused a dramatic decrease in catalytic efficiency. Mutation of Gly to Val in one subunit also yielded an enzyme with very low activity. The enzymes containing Thr-->Asn and Gly-->Val mutations in both subunits resulted in inactive enzymes, based on their inability to self-process and on assay with an oligopeptide substrate. The dramatic decrease in enzyme efficiency of the mutants was interpreted using molecular models of the enzymes.
Bagossi
P
P
Department of Biochemistry, University Medical School of Debrecen, Hungary.
Cheng
Y S
YS
Oroszlan
S
S
Tözsér
J
J
D001224:Aspartic Acid / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019281:Dimerization; D005813:Genes, Synthetic; D005998:Glycine / Q000235:genetics; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D007700:Kinetics; D008958:Models, Molecular; D016296:Mutagenesis; D009842:Oligopeptides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000235:genetics
D009842:Oligopeptides; D013912:Threonine; D001224:Aspartic Acid; D016333:HIV Protease; D005998:Glycine