Effector analogues detect varied allosteric roles for conserved protein-effector interactions in pyruvate kinase isozymes.
The binding site for allosteric inhibitor (amino acid) is highly conserved between human liver pyruvate kinase (hL-PYK) and the rabbit muscle isozyme (rM(1)-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 rM(1)-PYK. In hL-PYK, the minimum chemical requirements for effector binding are the same as those identified for rM(1)-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 rM(1)-PYK. This finding is inconsistent with the idea that allosteric pathways are conserved between homologues of a protein family.
Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, MS 3030, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, United States.
Aileen Y
AY
Alontaga
Aron W
AW
Fenton
D000494:Allosteric Regulation; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011487:Protein Conformation; D011770:Pyruvate Kinase / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits
D000596:Amino Acids; D007527:Isoenzymes; D011770:Pyruvate Kinase
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