Please use this identifier to cite or link to this item:
|Title:||PKR-inhibitor binds efﬁciently with human microtubule afﬁnity-regulating kinase 4||Authors:||Naz, Farha
Hassan, Md. Imtaiyaz
|Keywords:||PKR-inhibitor;MAP/microtubule afﬁnity-regulating kinase 4;Docking;Drug target;High afﬁnity ligand;Molecular dynamics simulation||Issue Date:||2015||Publisher:||Elsevier||Source:||Naz, F. et al. 2015. PKR-inhibitor binds efﬁciently with human microtubule afﬁnity-regulating kinase 4. Journal of Molecular Graphics and Modelling, 62: 245-252.||Abstract:||MAP/microtubule afﬁnity-regulating kinase 4 (MARK4) plays a central role in the cellular physiology, and it is inseparably linked with many human diseases including cancer, diet induced obesity, type2 diabetes and neurodegenerative disorders. Here, we studied the interaction of PKR-inhibitor with two variants of human MARK4. One variant is named as MARK4-F1 which has 59 N-terminal residues along with kinase domain while another variant is MARK4-F2 which has kinase domain only. Molecular-docking, molecular dynamics (MD) simulation and ﬂuorescence-binding studies were undertaken to understand the role of N-terminal 59-residues in the binding of substrate/inhibitors. Molecular docking studies revealed that the PKR-inhibitor binds in the large hydrophobic cavity of the kinase domain of MARK4 through several hydrophobic and hydrogen-bonded interactions. Furthermore, MD simulation showed a stable param-eters for the complexes of both MARK4-F1 and MARK4-F2 to PKR-inhibitor with marginal difference in their binding afﬁnities. A signiﬁcant decrease in the ﬂuorescence intensity of MARK4 was observed on successive addition of the PKR-inhibitor. Using ﬂuorescence data we have calculated the binding-afﬁnity and the number of binding site of PKR-inhibitor to the MARK4. A signiﬁcantly high binding afﬁnity was observed for the PKR-inhibitor to the MARK4 variants. However, there is no any signiﬁcant difference in the binding afﬁnity of PKR-inhibitor to the MARK4 variants was observed, indicating that 59 N-terminal residues of MARK4-F1 are not playing a crucial role in the ligand binding. The present study will pro-vide an insights into designing of new PKR-inhibitor derivative as potent and selective therapeutic agent against many life threatening diseases which are associated with MARK4.||URI:||http://hdl.handle.net/10321/1609||ISSN:||1093-3263|
|Appears in Collections:||Research Publications (Applied Sciences)|
Show full item record
checked on Nov 20, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.