Phosphatase Subfamily PGAM

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily PGAM

Domain

PGAM has single domain, phosphatase domain of HP1 family.

Catalytic activity

Human has four members:

• BPGM: 2,3-bisphosphoglycerate mutase. Bisphosphoglycerate mutase is an erythrocyte-specific en- zyme catalyzing a series of intermolecular phosphoryl group transfer reactions. Its main function is to synthesize 2,3- bisphosphoglycerate [1, 2].
• PGAM1: phosphoglycerate mutase 1 (brain). Glycolytic enzyme PGAM1 regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth. This is the mechanism behind oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells [3, 4]. NAD+-dependent deacetylase Sirt1 deacetylates phosphoglycerate mutase-1 (PGAM1) and attenuates catalytic activity [5].
• PGAM2: phosphoglycerate mutase 2 (muscle). Glycolytic enzyme PGAM expressed in muscle [6].
• PGAM4 (aka PGAM3): phosphoglycerate mutase family member 4.