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

被引:33
作者
Ascenzi, Paolo [1 ,2 ,3 ]
di Masi, Alessandra [1 ,2 ]
De Sanctis, Giampiero [4 ]
Coletta, Massimo [5 ]
Fasano, Mauro [6 ,7 ]
机构
[1] Univ Roma Tre, Dept Biol, I-00146 Rome, Italy
[2] Univ Roma Tre, Interdept Lab Electron Microscopy, I-00146 Rome, Italy
[3] IRCCS Lazzaro Spallanzani, Natl Inst Infect Dis, I-00149 Rome, Italy
[4] Univ Camerino, Dept Mol Cellular & Anim Biol, I-62032 Camerino, MC, Italy
[5] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
[6] Univ Insubria, Dept Struct & Funct Biol, I-21052 Busto Arsizio, VA, Italy
[7] Univ Insubria, Ctr Neurosci, I-21052 Busto Arsizio, VA, Italy
关键词
Ferrous nitrosylated human serum; heme-albumin; Ibuprofen-dependent denitrosylation; Ibuprofen-dependent absorbance spectroscopic properties; Kinetics; Thermodynamics; Allostery; PERFORMANCE AFFINITY-CHROMATOGRAPHY; DRUG-BINDING; CRYSTAL-STRUCTURE; CRYSTALLOGRAPHIC ANALYSIS; ENZYMATIC-PROPERTIES; ATOMIC-STRUCTURE; STRUCTURAL BASIS; LIGAND-BINDING; IRON GEOMETRY; NITRIC-OXIDE;
D O I
10.1016/j.bbrc.2009.06.117
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human 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) x 10(-4) s(-1), in the absence of the drug, to (9.5 +/- 1.2) x 10(-3) s(-1), in the presence of 1.0 x 10(-2) M ibuprofen, at pH 7.0 and 10.0 degrees C. From the dependence of k(off) on the drug concentration, values of the dissociation equilibrium constant for ibuprofen binding to to HSA-heme-Fe(II)-NO (K(1) = (3.1 +/- 0.4) x 10(-7) M, K(2)= (1.7 +/- 0.2) x 10(-4) M. and K(3) (2.2 +/- .2) x 10(-3) M) were determined. The K(3) value corresponds to the HSA-heme-Fe(II)-NO determined by monitoring drug-dependent absorbance spectroscopic changes (H = (2.6 +/- 0.3) x 10(-3) 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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:83 / 86
页数:4
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