Distinguishing the interactions in the fructose 1,6-bisphosphate binding site of human liver pyruvate kinase that contribute to allostery.
Kansas City, United States. In Biochemistry, Mar 2015
The antihyperglycemic target, human liver pyruvate kinase (hL-PYK), binds its allosteric activator, fructose 1,6-bisphosphate (Fru-1,6-BP), such that the 1'-phosphate interacts with side chains of Arg501 and Trp494 and the 6'-phosphate interacts with Thr444, Thr446, Ser449 (i.e., the 444-449 loop), and Ser531.
Structures of pyruvate kinases display evolutionarily divergent allosteric strategies.
Edinburgh, United Kingdom. In R Soc Open Sci, 2014
The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces.
Phosphorylase Kinase Deficiency
Seattle, United States. In Unknown Journal, 2011
Mutations in PHKA1, encoding subunit α, cause the rare X-linked disorder muscle PhK deficiency; mutations in PHKA2, also encoding subunit α, cause the most common form, liver PhK deficiency (X-linked liver glycogenosis); mutations in PHKB, encoding subunit β, cause autosomal recessive PhK deficiency in both liver and muscle; and mutations in PHKG2, encoding subunit γ, cause autosomal recessive liver PhK deficiency.
HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms.
Mexico. In Mini Rev Med Chem, 2009
In cancer cells, HIF-1alpha induces over-expression and increased activity of several glycolytic protein isoforms that differ from those found in non-malignant cells, including transporters (GLUT1, GLUT3) and enzymes (HKI, HKII, PFK-L, ALD-A, ALD-C, PGK1, ENO-alpha, PYK-M2, LDH-A, PFKFB-3).