Open AccessEffect of pH on the structure and function of cyclin-dependent kinase 6
Author(s) -
Mohd Yousuf,
Anas Shamsi,
Farah Anjum,
Alaa Shafie,
Asimul Islam,
Qazi Mohd Rizwanul Haque,
Abdelbaset Mohamed Elasbali,
Dharmendra Kumar Yadav,
Md. Imtaiyaz Hassan
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0263693
Subject(s) - cyclin dependent kinase 6 , circular dichroism , chemistry , cyclin dependent kinase , kinase , biochemistry , biophysics , protein secondary structure , enzyme , protein tertiary structure , microbiology and biotechnology , cyclin dependent kinase 2 , biology , protein kinase a , apoptosis , cell cycle
Cyclin - dependent kinase 6 (CDK6) is an important protein kinase that regulates cell growth, development, cell metabolism, inflammation, and apoptosis. Its overexpression is associated with reprogramming glucose metabolism through alternative pathways and apoptosis, which ultimately plays a significant role in cancer development. In the present study, we have investigated the structural and conformational changes in CDK6 at varying pH employing a multi-spectroscopic approach. Circular dichroism (CD) spectroscopy revealed at extremely acidic conditions (pH 2.0–4.0), the secondary structure of CDK6 got significantly disrupted, leading to aggregates formation. These aggregates were further characterized by employing Thioflavin T (ThT) fluorescence. No significant secondary structural changes were observed over the alkaline pH range (pH 7.0–11.0). Further, fluorescence and UV spectroscopy revealed that the tertiary structure of CDK6 was disrupted under extremely acidic conditions, with slight alteration occurring in mild acidic conditions. The tertiary structure remains intact over the entire alkaline range. Additionally, enzyme assay provided an insight into the functional aspect of CDK at varying pH; CDK6 activity was optimal in the pH range of 7.0–8.0. This study will provide a platform that provides newer insights into the pH-dependent dynamics and functional behavior of CDK6 in different CDK6 directed diseased conditions, viz. different types of cancers where changes in pH contribute to cancer development.