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Titolo:
Effect of ibuprofen and warfarin on the allosteric properties of haem-human serum albumin - A spectroscopic study
Autore:
Baroni, S; Mattu, M; Vannini, A; Cipollone, R; Aime, S; Ascenzi, P; Fasano, M;
Indirizzi:
Univ Insubria, Dept Struct & Funct Biol, I-21100 Varese, Italy Univ Insubria Varese Italy I-21100 t & Funct Biol, I-21100 Varese, Italy Univ Turin, Dept Chem IFM, I-10124 Turin, Italy Univ Turin Turin Italy I-10124 urin, Dept Chem IFM, I-10124 Turin, Italy Univ Roma Tre, Dept Biol, Rome, Italy Univ Roma Tre Rome ItalyUniv Roma Tre, Dept Biol, Rome, Italy
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 23, volume: 268, anno: 2001,
pagine: 6214 - 6220
SICI:
0014-2956(200112)268:23<6214:EOIAWO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
FERROUS HUMAN ADULT; HUMAN HEMOGLOBIN; T-STATE; CRYSTAL-STRUCTURE; LIGAND-BINDING; PROTEIN; STABILIZATION; RESOLUTION; MECHANISMS; KINETICS;
Keywords:
allostery; haem-human serum albumin; human serum albumin; ibuprofen; warfarin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Fasano, M Univ Insubria, Dept Struct & Funct Biol, Via Jean H Dunant 3, I-21100 Varese, Italy Univ Insubria Via Jean H Dunant 3 Varese Italy I-21100e, Italy
Citazione:
S. Baroni et al., "Effect of ibuprofen and warfarin on the allosteric properties of haem-human serum albumin - A spectroscopic study", EUR J BIOCH, 268(23), 2001, pp. 6214-6220

Abstract

Haem binding to human serum albumin (HSA) endows the protein with peculiarspectroscopic properties. Here, the effect of ibuprofen and warfarin on the spectroscopic properties of ferric haem-human serum albumin (ferric HSA-haem) and of ferrous nitrosylated haem-human serum albumin (ferrous HSA-haem-NO) is reported. Ferric HSA-haem is hexa-coordinated, the haem-iron atom being bonded to His105 and Tyr148. Upon drug binding to the warfarin primarysite, the displacement of water molecules - buried in close proximity to the haem binding pocket - induces perturbation of the electronic absorbance properties of the chromophore without affecting the coordination number or the spin state of the haem-iron, and the quenching of the H-1-NMR relaxivity. Values of K-d for ibuprofen and warfarin binding to the warfarin primarysite of ferric HSA-haem, corresponding to the ibuprofen secondary cleft, are 5.4 +/- 1.1 x 10(-4) rm and 2.1 +/- 0.4 x 10(-5) M, respectively. The affinity of ibuprofen and warfarin for the warfarin primary cleft of ferric HSA-haem is lower than that reported for drug binding to haem-free HSA. Accordingly, the K-d value for haem binding to HSA increases from 1.3 +/- 0.2 x10(-8) m in the absence of drugs to 1.5 +/- 0.2 x 10(-7) M in the presenceof ibuprofen and warfarin. Ferrous HSA-haem-NO is a five-coordinated haem-iron system. Drug binding to the warfarin primary site of ferrous HSA-haem-NO induces the transition towards the six-coordinated haem-iron species, the haem-iron atom being bonded to His105. Remarkably, the ibuprofen primary cleft appears to be functionally and spectroscopically uncoupled from the haem site of HSA. Present results represent a clear-cut evidence for the drug-induced shift of allosteric equilibrium(a) of HSA.

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Documento generato il 11/07/20 alle ore 17:44:18