Functional Relevance of Human Pyruvate Kinase-M2 Mutations

Language: English

Published by LAP LAMBERT Academic Publishing Feb 2012, 2012

3848408961 / 9783848408962

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This item is printed on demand - Print on Demand Titel. Neuware -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.VDM Verlag, Dudweiler Landstraße 99, 66123 Saarbrücken 100 pp. Englisch.…

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Title
Functional Relevance of Human Pyruvate Kinase-M2 Mutations
Author
Vibhor Gupta
Publisher
LAP LAMBERT Academic Publishing Feb 2012
Publication year
2012
Condition
Neu
Binding
Taschenbuch
Language
English
ISBN 10
3848408961
ISBN 13
9783848408962
Item weight
167 grams
Dimensions
220x150x6 mm

buchversandmimpf2000

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