An allostatic mechanism for M2 pyruvate kinase as an amino-acid sensor.

ABSTRACT: We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that, within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors, while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer-monomer dissociation K_d is estimated to be ∼0.9 µM with a slow dissociation rate (t_1/2∼15 min). X-ray structures of M2PYK complexes with alanine, phenylalanine, and tryptophan show the M2PYK locked in an inactive T-state con

SUBMITTER: Yuan M 

PROVIDER: S-EPMC5980995 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature