Esterase-Like Activity of Serum Albumin: Characterization of Its Structural Chemistry Using p-Nitrophenyl Esters as Substrates

Sakurai, Yuji; Feng, Shen; Watanabe, Hiroshi; Yamaotsu, Noriyuki; Hirono, Shuichi; Kurono, Yukihisa; Kragh‐Hansen, Ulrich; Otagiri, Masaki

doi:10.1023/b:pham.0000016241.84630.06

Cited by 126 publications

(144 citation statements)

References 14 publications

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“…Among others, HSA appears (1) to be an important determinant of the pharmacokinetic behavior of many drugs, (2) to account for most of the antioxidant capacity of human serum, and (3) to display enzymatic properties [1][2][3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Evidence for pH-dependent multiple conformers in iron(II) heme–human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding

et al. 2011

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Section: Introductionmentioning

confidence: 99%

Evidence for pH-dependent multiple conformers in iron(II) heme–human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding

et al. 2011

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“…Moreover, HSA affects pharmacokinetics of many drugs, holds some ligands in a strained orientation, providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and displays (pseudo-)enzymatic properties [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

mentioning

confidence: 99%

“…Terminal regions of sequential domains contribute to the formation of interdomain helices linking domain IB to IIA, and IIB to IIIA (Fig. 1) [2,3,6,8,12,14,15,[17][18][19][20][21][22][23][24][25].…”

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confidence: 99%

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Ibuprofen modulates allosterically NO dissociation from ferrous nitrosylated human serum heme-albumin by binding to three sites

Ascenzi

Masi

Sanctis

et al. 2009

Biochemical and Biophysical Research Communications

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a b s t r a c tHuman serum albumin (HSA) is a monomeric allosteric protein. Here, the effect of ibuprofen on denitrosylation kinetics (k off ) and spectroscopic properties of HSA-heme-Fe(II)-NO is reported. The k off value increases from (1.4 ± 0.2) Â 10 À4 s À1 , in the absence of the drug, to (9.5 ± 1.2) Â 10 À3 s À1 , in the presence of 1.0 Â 10 À2 M ibuprofen, at pH 7.0 and 10.0°C. From the dependence of k off on the drug concentration, values of the dissociation equilibrium constants for ibuprofen binding to HSA-heme-Fe(II)-NO (K 1 = (3.1 ± 0.4) Â 10 À7 M, K 2 = (1.7 ± 0.2) Â 10 À4 M, and K 3 = (2.2 ± 0.2) Â 10 À3 M) were determined. The K 3 value corresponds to the value of the dissociation equilibrium constant for ibuprofen binding to HSA-heme-Fe(II)-NO determined by monitoring drug-dependent absorbance spectroscopic changes (H = (2.6 ± 0.3) Â 10 À3 M). Present data indicate that ibuprofen binds to the FA3-FA4 cleft (Sudlow's site II), to the FA6 site, and possibly to the FA2 pocket, inducing the hexa-coordination of HSA-heme-Fe(II)-NO and triggering the heme-ligand dissociation kinetics.

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“…Human serum albumin (HSA), the most prominent protein in plasma, provides a depot and carrier for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders harmless potential toxins transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and displays (pseudo-)enzymatic properties [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

mentioning

confidence: 99%

Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin

Ascenzi

Imperi

Coletta

et al. 2008

Biochemical and Biophysical Research Communications

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Human serum albumin (HSA) participates to heme scavenging, in turn HSA-heme binds gaseous diatomic ligands at the heme-Featom. Here, the effect of abacavir and warfarin on denitrosylation kinetics of HSA-heme-Fe(II)-NO (i.e., k off ) is reported. In the absence of drugs, the value of k off is (1.3 ± 0.2) Â 10 À4 s À1 . Abacavir and warfarin facilitate NO dissociation from HSA-heme-Fe(II)-NO, the k off value increases to (8.6 ± 0.9) Â 10 À4 s À1 . From the dependence of k off on the drug concentration, values of the dissociation equilibrium constant for the abacavir and warfarin binding to HSA-heme-Fe(II)-NO (i.e., K = (1.2 ± 0.2) Â 10 À3 M and (6.2 ± 0.7) Â 10 À5 M, respectively) were determined. The increase of k off values reflects the stabilization of the basic form of HSA-heme-Fe by ligands (e.g., abacavir and warfarin) that bind to Sudlow's site I. This event parallels the stabilization of the six-coordinate derivative of the HSAheme-Fe(II)-NO atom. Present data highlight the allosteric modulation of HSA-heme-Fe(II) reactivity by heterotropic effectors.

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Esterase-Like Activity of Serum Albumin: Characterization of Its Structural Chemistry Using p-Nitrophenyl Esters as Substrates

Abstract: The results are consistent with a scenario in which HSA becomes acylated due to a nucleophilic attack by Tyr-411 on the substrate and then is deacylated by general acid or base catalysis with the participation of water.

Cited by 126 publications

References 14 publications

Evidence for pH-dependent multiple conformers in iron(II) heme–human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding

Evidence for pH-dependent multiple conformers in iron(II) heme–human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding

Ibuprofen modulates allosterically NO dissociation from ferrous nitrosylated human serum heme-albumin by binding to three sites

Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin

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