Functional Relevance of Human Pyruvate Kinase-M2 Mutations: PKM2 Mutations from Bloom Syndrome patients - Softcover

Gupta, Vibhor; Bamezai, Rameshwar N.K.

Softcover

ISBN 10: 3848408961 ISBN 13: 9783848408962

Publisher: LAP LAMBERT Academic Publishing, 2012

Synopsis

Out of 4 isoforms of Pyruvate kinase; a glycolytic enzyme, M2 is a prototype isoform expressed in embryonic and adult dividing cells. For the first time, we reported two missense mutations in Pyruvate kinase M2 isozyme (H391Y and K422R) from the cells of Bloom syndrome patients, prone to develop cancer. Results showed that despite the presence of mutations in the inter-subunit contact domain, the K422R and H391Y mutant proteins maintained their homotetrameric structure, similar to the wild-type protein, but showed a loss of activity by 75 and 20%, respectively. Interestingly, H391Y showed a 6-fold increase in affinity for its substrate phosphoenolpyruvate and behaved like a non-allosteric protein with compromised cooperative binding. The co-expression of homotetrameric wild type and mutant PKM2 in the cellular milieu resulted in the interaction between the two at the monomer level, which was substantiated further by in vitro experiments. Interestingly, in a unique observation, hetero-oligomeric populations of PKM2 with an altered activity and affinity led to an increased rate of polyploidy i.e genomic instability.

About this title

About the Author

Dr. Gupta graduated as a Gold Medalist from Himachal Pradesh University, in year 2005 and joined Jawaharlal Nehru University for his PhD. He was awarded with the degree of doctor of philosophy in year 2010. At the time of publication of this book, he is working as a Postdoctoral fellow in University of Pennsylvania, USA.

Edition details

• Publisher: LAP LAMBERT Academic Publishing
• Publication date: 2012
• ISBN 10: 3848408961
• ISBN 13: 9783848408962
• Binding: Paperback
• Language: English
• Number of pages: 100