The extraordinary ligand binding properties of human serum albumin

Abstract

SummaryHuman serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, 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 acts as a NO-carrier. The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins. Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized. IUBMB Life, 57: 787 -796, 2005

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

“…In addition, the growing importance of the diatomic ligand CO as a gas transducer involved in the signaling related to reactive oxygen species [60] renders these kinetic investigations of physiopathological relevance. Thus, the role played by heme-HSA in the detoxification process is significantly enhanced by the fact that the amount of heme-HSA increases significantly under pathological conditions [9,10,61,62] owing to the function of HSA as a heme scavenger from HDL and LDL, impairing their oxidation [8,48,49].…”

“…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].…”

Reversible two-step unfolding of heme–human serum albumin: a 1H-NMR relaxometric and circular dichroism study

“…1). In sites FA1-FA5 the carboxylate moiety of FAs is anchored by electrostatic/polar interactions; in contrast, sites FA6 and FA7 do not display clear evidence of polar interactions that keep in place the carboxylate head of the FA, thus suggesting that sites FA6 and FA7 are low-affinity FA binding sites [3,4,[6][7][8][9][10]. One of the FA binding sites (FA1) has evolved to selectively bind heme with high affinity (K d = 1.0 9 10 -8 M [11]) with the tetrapyrrole ring arranged in a D-shaped cavity limited by Tyr138 and Tyr161 residues that provide p-p stacking interaction with the porphyrin and supply a donor oxygen (from Tyr161) for the Fe(III) heme iron [10][11][12][13][14].…”

“…Each domain is formed by two separate subdomains (named A and B), connected by a random coil (Fig. 1) [1][2][3][4][5].…”

“…One of the FA binding sites (FA1) has evolved to selectively bind heme with high affinity (K d = 1.0 9 10 -8 M [11]) with the tetrapyrrole ring arranged in a D-shaped cavity limited by Tyr138 and Tyr161 residues that provide p-p stacking interaction with the porphyrin and supply a donor oxygen (from Tyr161) for the Fe(III) heme iron [10][11][12][13][14]. In turn, heme binding to HSA endows the protein with heme-based reactivity [4,15] and spectroscopic properties [16][17][18][19][20][21].…”