4GPI: Crystal Structure Of Human B Type Phosphoglycerate Mutase

Citation:
Abstract
How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear. We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. Moreover, 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. As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation.
PDB ID: 4GPIDownload
MMDB ID: 110272
PDB Deposition Date: 2012/8/21
Updated in MMDB: 2013/05
Experimental Method:
x-ray diffraction
Resolution: 2.08  Å
Source Organism:
Similar Structures:
Biological Unit for 4GPI: dimeric; determined by author and by software (PISA)
Molecular Components in 4GPI
Label Count Molecule
Proteins (2 molecules)
2
Phosphoglycerate Mutase 1(Gene symbol: PGAM1)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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