Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin.

Article Details

Citation

Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P

Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin.

FEBS J. 2005 Dec;272(24):6287-96.

PubMed ID
16336266 [ View in PubMed
]
Abstract

Human serum albumin (HSA), the most prominent protein in plasma, is best known for its exceptional capacity to bind ligands (e.g. heme and drugs). Here, binding of the anti-HIV drugs abacavir, atazanavir, didanosine, efavirenz, emtricitabine, lamivudine, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, and zidovudine to HSA and ferric heme-HSA is reported. Ferric heme binding to HSA in the absence and presence of anti-HIV drugs was also investigated. The association equilibrium constant and second-order rate constant for the binding of anti-HIV drugs to Sudlow's site I of ferric heme-HSA are lower by one order of magnitude than those for the binding of anti-HIV drugs to HSA. Accordingly, the association equilibrium constant and the second-order rate constant for heme binding to HSA are decreased by one order of magnitude in the presence of anti-HIV drugs. In contrast, the first-order rate constant for ligand dissociation from HSA is insensitive to anti-HIV drugs and ferric heme. These findings represent clear-cut evidence for the allosteric inhibition of anti-HIV drug binding to HSA by the heme. In turn, anti-HIV drugs allosterically impair heme binding to HSA. Therefore, Sudlow's site I and the heme cleft must be functionally linked.

DrugBank Data that Cites this Article

Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
AtazanavirSerum albuminProteinHumans
Unknown
Binder
Details
DidanosineSerum albuminProteinHumans
Unknown
Not AvailableDetails
EfavirenzSerum albuminProteinHumans
Unknown
Not AvailableDetails
EmtricitabineSerum albuminProteinHumans
Unknown
Binder
Details
LamivudineSerum albuminProteinHumans
Unknown
Not AvailableDetails
NelfinavirSerum albuminProteinHumans
Unknown
Not AvailableDetails
NevirapineSerum albuminProteinHumans
Unknown
Not AvailableDetails
RitonavirSerum albuminProteinHumans
Unknown
Substrate
Details
StavudineSerum albuminProteinHumans
Unknown
Not AvailableDetails