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Effector Analogues Detect Varied Allosteric Roles for Conserved Protein−Effector Interactions in Pyruvate Kinase Isozymes

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journal contribution
posted on 2011-03-22, 00:00 authored by Aileen Y. Alontaga, Aron W. Fenton
The binding site for allosteric inhibitor (amino acid) is highly conserved between human liver pyruvate kinase (hL-PYK) and the rabbit muscle isozyme (rM1-PYK). To detail similarities/differences in the allosteric function of these two homologues, we quantified the binding of 45 amino acid analogues to hL-PYK and their allosteric impact on affinity for the substrate, phosphoenolpyruvate (PEP). This complements a similar study previously completed for rM1-PYK. In hL-PYK, the minimum chemical requirements for effector binding are the same as those identified for rM1-PYK (i.e., the l-2-aminopropanaldehyde substructure of the effector is primarily responsible for binding). However, different regions of the effector determine the magnitude of the allosteric response in hL-PYK vs rM1-PYK. This finding is inconsistent with the idea that allosteric pathways are conserved between homologues of a protein family.