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Single amino acid substitution in HIV‐1 integrase catalytic core causes a dramatic shift in inhibitor selectivity
Author(s) -
Al-Mawsawi Laith Q.,
Sechi Mario,
Neamati Nouri
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.02.023
Subject(s) - integrase , chemistry , selectivity , dna , serine , stereochemistry , active site , catalysis , combinatorial chemistry , biochemistry , enzyme
HIV‐1 integrase (IN) mediates the insertion of viral cDNA into the cell genome, a vital process for replication. This step is catalyzed by two separate DNA reaction events, termed 3′‐processing and strand transfer. Here, we show that six inhibitors from five structurally different classes of compounds display a selectivity shift towards preferential strand transfer inhibition over the 3′‐processing activity of IN when a single serine is substituted at position C130. Even though IN utilizes the same active site for both reactions, this finding suggests a distinct conformational dissimilarity in the mechanistic details of each IN catalytic event.