title: Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: insight into integrase-DNA complex formation and catalysis.
abstract: A lens epithelium-derived growth factor (LEDGF)/p75 peptide was evaluated for human immunodeficiency virus type 1 integrase (IN) inhibitory activity. The LEDGF/p75 peptide modestly inhibited IN catalysis and was dependent on IN-DNA assembly. The peptide was also effective at disrupting LEDGF/p75-IN complex formation. We next investigated the activity of the LEDGF/p75 peptide on IN mutant proteins that are unable to catalyze the DNA strand transfer reaction. The LEDGF/p75 peptide displayed an increased potency on these IN proteins, from 5-fold to greater than 10-fold, indicating the IN multimeric state greatly influences the peptide inhibitory effects. These results shed light on IN-DNA multimeric formation, and how this process influences the LEDGF/p75-IN interaction.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Laith Q
authors.initials: LQ
authors.lastname: Al-Mawsawi
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Raveendra
authors.initials: R
authors.lastname: Dayam
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D019427:HIV Integrase / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D019428:HIV Integrase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C119380:lens epithelium-derived growth factor; D004247:DNA; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1