Investigating the binding affinities of fructose and galactose to human serum albumin: simulation studies.

Human serum albumin (HSA) is abundant in blood. HSA binds a wide range of drugs, metabolites, and nutrients. A glycated HSA is also a potential diabetes biomarker. Recently, crystal structures of glucose- and fructose-bound HSA have been reported. Both cyclic and acyclic sugar forms are trapped in Sudlow site I. Galactose can also bind HSA, but no atomic detail is available. Thus, molecular dynamics simulations were employed to study the structural and dynamic properties of fructose- and galactose-bound HSA in comparison to glucose-bound HSA from previous studies. Both bound sugars promote different degrees of domain motions which can affect a drug/solute binding affinity at Sudlow site I. A large and highly water-exposed Sudlow site I allows high mobility of bound sugars. Nonetheless, more protein contacts imply a tighter binding of fructose than galactose. Although galactose and glucose are epimers, galactose forms a different interaction network which disrupts a formation of interactions with K195 and K199 resulting in the escape of galactose. In contrast, fructose molecules are anchored inside by a number of protein interactions and sugar dimer structure. These highlights the importance of protein–sugar and sugar–sugar interactions for ligand binding in large and highly water-exposed cavity. [ABSTRACT FROM AUTHOR]