Molecular and enzoinformatics perspectives of targeting Polo-like kinase 1 in cancer therapy

Publication date: Available online 6 November 2017 Source:Seminars in Cancer Biology Author(s): Shazi Shakil, Mohammad H. Baig, Shams Tabrez, Syed M. Danish Rizvi, Syed K. Zaidi, Ghulam M. Ashraf, Shakeel A. Ansari, Aftab Aslam Parwaz Khan, Mohammad H. Al-Qahtani, Adel M. Abuzenadah, Adeel G. Chaudhary Cancer is a disease that has been the focus of scientific research and discovery and continues to remain so. Polo-like kinases (PLKs) are basically serine/threonine kinase enzymes that control cell cycle from yeast to humans. PLK-1 stands for ‘Polo-like kinase-1’. It is the most investigated protein among PLKs. It is crucial for intracellular processes, hence a ‘hot’ anticancer drug-target. Accelerating innovations in Enzoinformatics and associated molecular visualization tools have made it possible to literally perform a ‘molecular level walk’ traversing through and observing the minutest contours of the active site of relevant enzymes. PLK-1 as a protein consists of a kinase domain at the protein N-terminal and a Polo Box Domain (PBD) at the C-terminal connected by a short inter-domain linking region. PBD has two Polo-Boxes. PBD of PLK-1 gives the impression of “a small clamp sandwiched between two clips”, where the two Polo Boxes are the ‘clips’ and the ‘phosphopeptide’ is the small ‘clamp’. Broadly, two major sites of PLK-1 can be potential targets: one is the adenosine-5′-triphosphate (ATP)–binding site in the kinase domain and ...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research