Abstract
The robust structural nature of human serum albumin (HSA) is responsible for its multifarious functional property. The site specific glycation of HSA due to hyperglycaemia (excess glucose) causes structural changes which have an impact on the functioning of the protein. This work investigates the effects of glucose-mediated glycation in the altered inter-domain motion, distorted binding site conformation and modified hydration patterns, Trp214 orientation, and secondary structure transition using simulation approach. Here we have observed an increase of turns in the helices of glycated HSA, which modulates the open-close conformation of Sudlow I & II. The secondary structure changes of glycated HSA indicate plausible reduction in the alpha helical content in the helices which participates in ligand binding. It also affects geometrical features of drug binding sites (Sudlow I and II) such as volume and hydration. We found that glycation disturbs domain specific mobility patterns of HSA, a substantial feature for albumin drug binding ability which is also correlated with changes in the local environment of Trp214.
Communicated by Ramaswamy H. Sarma
Acknowledgments
Authors thank the Department of Biotechnology (DBT), Government of India (BT/PR9167/BRB/10/1268/2013) for the funding. We thank Bioinformatics Resource and Applications Facility (BRAF) at Centre for Development of Advanced Computing, Pune, India for providing the supercomputing facility. Jayanth thanks Council for Scientific and Industrial Research (CSIR), Government of India for the award of Senior Research Fellowship (File No: 09/1095(0052)/2020-EMR-I) and we thank SASTRA University for the infrastructure.
Disclosure statement
The authors declare that they have no conflicts of interest.