Download MendeleyChanges in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation-pi bond.
McFarlane, J.S., Ronnebaum, T.A., Meneely, K.M., Chilton, A., Fenton, A.W., Lamb, A.L.(2019) Acta Crystallogr F Struct Biol Commun 75: 461-469
- PubMed: 31204694
- DOI: https://doi.org/10.1107/S2053230X19007209
- Primary Citation of Related Structures:
6NN4, 6NN5, 6NN7, 6NN8 - PubMed Abstract:
Human liver pyruvate kinase (hLPYK) converts phosphoenolpyruvate to pyruvate in the final step of glycolysis. hLPYK is allosterically activated by fructose-1,6-bisphosphate (Fru-1,6-BP). The allosteric site, as defined by previous structural studies, is located in domain C between the phosphate-binding loop (residues 444-449) and the allosteric loop (residues 527-533). In this study, the X-ray crystal structures of four hLPYK variants were solved to make structural correlations with existing functional data. The variants are D499N, W527H, Δ529/S531G (called GGG here) and S531E. The results revealed a conformational toggle between the open and closed positions of the allosteric loop. In the absence of Fru-1,6-BP the open position is stabilized, in part, by a cation-π bond between Trp527 and Arg538' (from an adjacent monomer). In the S531E variant glutamate binds in place of the 6'-phosphate of Fru-1,6-BP in the allosteric site, leading to partial allosteric activation. Finally, the structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant.
- Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside, Lawrence, KS 66045, USA.
Organizational Affiliation:
