Changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation – π bond

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, Δ 529/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.

Source: Acta Crystallographica Section F - June 9, 2019 Category: Biochemistry Authors: McFarlane, J.S. Ronnebaum, T.A. Meneely, K.M. Chilton, A. Fenton, A.W. Lamb, A.L. Tags: pyruvate kinase allosterism human liver isozyme research communications Source Type: research