L-chicoric acid inhibits human immunodeficiency virus type 1 integration in vivo and is a noncompetitive but reversible inhibitor of HIV-1 integrase in vitro.
The human immunodeficiency virus (HIV) integrase (IN) must covalently join the viral cDNA into a host chromosome for productive HIV infection. l-Chicoric acid (l-CA) enters cells poorly but is a potent inhibitor of IN in vitro. Using quantitative real-time polymerase chain reaction (PCR), l-CA inhibits integration at concentrations from 500 nM to 10 microM but also inhibits entry at concentrations above 1 microM. Using recombinant HIV IN, steady-state kinetic analyses with l-CA were consistent with a noncompetitive or irreversible mechanism of inhibition. IN, in the presence or absence of l-CA, was successively washed. Inhibition of IN diminished, demonstrating that l-CA was reversibly bound to the protein. These data demonstrate that l-CA is a noncompetitive but reversible inhibitor of IN in vitro and of HIV integration in vivo. Thus, l-CA likely interacts with amino acids other than those which bind substrate.
Reinke
Ryan A
RA
Department of Microbiology and Molecular Genetics, University of California, Irvine 92697-4800, USA.
Lee
Deborah J
DJ
McDougall
Brenda R
BR
King
Peter J
PJ
Victoria
Joseph
J
Mao
Yingqun
Y
Lei
Xiangyang
X
Reinecke
Manfred G
MG
Robinson
W Edward
WE
D000090:Acetoacetates / Q000494:pharmacology; D001665:Binding Sites; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D020900:Echinacea; D019427:HIV Integrase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D011758:Pyrroles / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*; D016662:Virus Integration / Q000187:drug effects*
D000090:Acetoacetates; D002109:Caffeic Acids; D019428:HIV Integrase Inhibitors; C403886:L 731988; D011758:Pyrroles; D013386:Succinates; D019427:HIV Integrase; C100435:chicoric acid