The effect of full glycation on structure and function of human serum albumin

Human serum albumin (HSA) is the most abundant protein carrier found in blood. The level of glycated human serum albumin (GHSA) can be used as a diabetes biomarker. Therefore, many attempts have been made to design selective GHSA detection methods. GHSA has been found to show unique characteristics. Glycation has been found to impair albumin structure and function, where a microscopic explanation is limited. Thus, in this work, molecular dynamics simulations were performed to capture the structural and dynamic properties of GHSA in comparison to non-glycated albumin (HSA). A fully glycated albumin (experiment-reported 14 glycation sites) was used in this work. The changes in structural properties appear to be the root cause for functional impairment. The full glycation appears to cause: (i) the enhancement of protein flexibility and water exposure; (ii) the serious degrees of helical unfolding; (iii) the widening of drug site entrance; (iv) greater reactivity of C34 and (v) the severe alteration of fatty acid- and drug- binding cavities. Comparing with a single-site glycated albumin, the higher degrees of glycation appear to have more impact on protein structure and function. Our results can illustrate the key microscopic features that make GHSA differ from native HSA. This insight will aid in the design and development of selective and sensitive methods for GHSA detection.