Analysis of an alternatively spliced variant of mouse Pklr gene encoding a novel isoform with distinct N-terminal.

Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. Mammalian pyruvate kinase functions as a tetrameric protein composed of identical subunits, which adopt a dimer-of-dimers configuration. Each monomer features a single active site and consists of three primary domains designated A, B and C, and a small N-terminal domain. Alternative splicing generates four mammalian pyruvate kinase isoforms, namely, PKM1, PKM2, PKLR-1 and PKLR-2 with unique tissue expression patterns and regulatory properties. The PKLR-2 isoform is predominantly expressed in liver and is also present, though to a lesser extent, in the kidney. It is interesting to study the variation in different isoforms of pyruvate Kinase L/R gene and their involvement in regulation of various biological pathways. In the current study, using a combination of computational and molecular biology approaches, we have identified a novel alternatively spliced transcript of mouse pyruvate Kinase L/R gene, that has an alternate first exon and encodes 18-amino acid long peptide sequence at N-terminal. Structural differences between known and novel isoforms were evaluated via molecular modelling. MD simulation studies confirmed the overall stability of the new isoform under physiological conditions.