Allosteric Modulation Of Aurka Kinase Activity By Arkin-A Via Dynamic Correlation Network Analysis

• ORIGINAL ARTICLE | ISSUE DETAILS: VOL NO.3 | ISSUE NO. 1

Abstract

Protein phosphorylation and post-translational modification by protein kinases are crucial cell signaling and regulatory systems. AurkA, a serine/threonine kinase, controls mitotic cell division and has sequence homology with other kinases. Clinical trials are underway to target AurkA Kinase’s overexpression in human cancer using ATP-competitive drugs. AurkinA, a small allosteric inhibitor, binds to TPX2’s Y-pocket, which holds Y8 and Y10. AurkinA drug-like inhibitors delocalize the kinase from cell spindle formation, disrupting the Aurka–Tpx2 complex. The allosteric mechanism for these compounds is unclear at the molecular level. To understand the allosteric mechanism, all-atom molecular dynamics simulations were employed to create fluctuation association networks. The fluctuation correlation networks of AurkA-Tpx2 and AurkinA vary significantly. AurkA-AurkinA transfers information from the allosteric to the catalytic sites more readily than AurkA-Tpx2. These methods will help develop route-targeted drugs and create protein allosteric circuits.

Study Design: Molecular dynamics simulations, an investigative strategy, and AurkA kinase allostery.

Duration And Place Of Study: Department of Health, Medical Teaching Institution Mardan Medical Complex Mardan, form jan 2018 to jan 2019