In this section you are going to investigate two forms of py

In this section you are going to investigate two forms of pyruvate kinase, an enzyme from glycolysis that we will study in more detail later in the quarter. Pyruvate Kinase can be in an inactive T-state or an active R-state and is primarily activated by Fructose-1.6-bisphosphate. Below you will investigate two structures of pyruvate kinase, one with Fructose-1, 6-bisphosphate (4RPP) and one without

Solution

The distance between the aminoacids in a protein is determined by the resolution of the protein structure that is determined by certain physical methods like X-ray diffraction and NMR.

4RPP- 2.59A

4QGC – 2.3A

4RPP is different from 4QGC in one aminoacid residue. 4RPP has 536 residues and 4QGC has 535 residues. The mol.wt. of 4RPP is 236248.19 and that of 4QGC is 234764.17.

The residues that are helpful in the binding of FBP with the active site region of 4RPP are Ser402, Thr403, Ser404, Thr407, Asp455, His 491 and Arg459. The residues differing with the 4QGC structure that help in the binding of the ligand would differ.

Among the four isoforms of pyruvate kinase, M1 and M2 forms are generated from PKM gene by differential splicing. Isoform M2 is the source for 4RPP and 4QGC structures and is activated allosterically by Fructose 1,6 –bis phosphate (FBP). The binding of allosteric activator FBP to the tyrosine-phosphorylated peptides turn away glucose metabolites from energy production to other processes while the cells are triggered by the growth factors. Serine is considered as the natural ligand and allosteric activator of the M2 isoform.