Conformational variation of site specific glycated albumin: A Molecular dynamics approach

Jayanth Jeevanandam; V L S Prasad Burra; N T Saraswathi

doi:10.1016/j.compbiomed.2023.107276

Conformational variation of site specific glycated albumin: A Molecular dynamics approach

Comput Biol Med. 2023 Sep:164:107276. doi: 10.1016/j.compbiomed.2023.107276. Epub 2023 Jul 17.

Authors

Jayanth Jeevanandam¹, V L S Prasad Burra², N T Saraswathi³

Affiliations

¹ Molecular Biophysics lab, School of Chemical and Biotechnology, SASTRA Deemed to- be University, Thanjavur, 613401, Tamilnadu, India.
² Centre for Advanced Research and Innovation in Structural Biology of Diseases, K L E F (Deemed To Be) University, Vaddeswaram, Andhra Pradesh, 522 502, India.
³ Molecular Biophysics lab, School of Chemical and Biotechnology, SASTRA Deemed to- be University, Thanjavur, 613401, Tamilnadu, India. Electronic address: saras@scbt.sastra.edu.

PMID: 37481949
DOI: 10.1016/j.compbiomed.2023.107276

Abstract

Human serum albumin (HSA) is a major cargo protein, which undergoes glycation in hyperglycaemic conditions and results in impaired function. In physiological conditions, HSA plays a crucial role in pharmacological activities such as drug transport or delivery through its binding capacity and also by its enzymatic activity, which enables the translation of pro-drugs into active drugs. In this study, the impact of the methylglyoxal-mediated glycation on dynamic behaviour of inter-domain motion, Cys34 reactivity, binding site residual interaction and secondary structure transition were investigated through molecular dynamics simulation. The alteration in inter-domain motion reflects the effect of glycation-mediated changes on the structural conformation of albumin. The binding site residue interactions and volume analysis revealed the impact of glycation on the geometry of the binding site. We also found the correlation of Cys34 reactivity with increase of turns in the region between Ia-h4 and Ia-h5. The rise in turn formation in that region keeps Tyr84 farther away from Cys34 which could lead to higher Cys34 reactivity. In parallel, significant alterations in alpha helical content of helices in the binding sites were observed. These structural and conformational changes in glycated albumin could be the causative agents for functional impairment which leads to diabetic complications.

Keywords: Cys34 reactivity; Glycation; Human serum albumin; MGH1; Molecular dynamics; Structural and conformational analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Diabetes Complications*
Humans
Molecular Dynamics Simulation*
Protein Binding
Serum Albumin / chemistry
Serum Albumin, Human

Substances

Serum Albumin
Serum Albumin, Human