Prasoon Thakur1, Parvez Khan2, Faizan Ahmad2, Md. Imtaiyaz Hassan2
1Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
2Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
ABSTRACT
Hepcidin is a major regulator of iron metabolism. The alpha (2)-M (α2-M) is a major carrier in serum and proteinase inhibitor with broad specificity. The structural thioester of α2-M, is involved in the immobilization and entrapment of proteases. Recently, shown that hepcidin binds to α2-M in the blood, and such binding is crucial for iron homeostasis. Furthermore, hepcidin binding to α2-M also decreases the ferroportin expression. Therefore, we performed the docking studies on α2-M-hepcidin to understand the structural basis of such binding. The high resolution atomic coordinates of the receptor binding domain of α2-M (Residues 1-138) and hepcidin were retrieved from protein data bank. We used global and local docking of the hepcidin to α2-M which forms a strong stable complex. The stabilizing energy of this complex was found to be -473.065 kJ/mol which further suggests the formation of a strong and complex between α2-M and hepcidin. This was further supported by a large number of interactions formed between these proteins in complex form. The demonstration that α2-M is the hepcidin transporter could lead to better understanding of hepcidin therapeutic approach for the development of novel drugs for the treatment of iron-related ailments. Read more…
