Exploring how structural and dynamic properties of bovine and canine serum albumins differ from human serum albumin

Serum albumin (SA) is the most abundant protein in blood. SA carries a diverse range of nutrients and drugs. It has wide clinical and biochemical applications. Especially, administering human serum albumin (HSA) can increase albumin level and blood pressure in ill dogs and humans. Nonetheless, the use of HSA therapy is still controversial. Using albumin from other species is one of alternatives. Bovine serum albumin (BSA) is a homolog of HSA, but it shows different dynamics. Thus, understanding albumin properties from other species becomes crucial. Recently, the first crystal structure of canine serum albumin (CSA) has been solved. We thus employed Molecular Dynamics (MD) simulations to reveal structural and dynamic properties of CSA and BSA in comparison with HSA. The results indicate the motion of domains I and III is the key to define albumin characteristics. Among all, CSA is the most flexible. BSA and HSA are more alike in term of ligand-binding affinity. Many ligand-binding studies succeeded to employ BSA as a HSA substitute due to similar size and environment of binding pockets, however replacing HSA by BSA may fail in a dynamics-related process because of the more rigid BSA. For CSA, its properties deviate from BSA and HSA. CSA shows more flexibility and has larger and more water-exposed drug sites. Moreover, C34 on CSA is more reactive than that of BSA and HSA owing to more flexible side chain. An insight obtained can serve as a guideline for a future use of alternative albumins in clinical practice. (C) 2020 Elsevier Inc. All rights reserved.