biostudies-literatureWilkins JMNCCIH NIH HHSNational Institutes of Health25137-48https://www.ebi.ac.uk/biostudies/studies/S-EPMC4155678biostudies-literatureUnknown289(36)Phosphoglycerate mutase 5 (PGAM5) is an atypical mitochondrial Ser/Thr phosphatase that modulates mitochondrial dynamics and participates in both apoptotic and necrotic cell death. The mechanisms that regulate the phosphatase activity of PGAM5 are poorly understood. The C-terminal phosphoglycerate mutase domain of PGAM5 shares homology with the catalytic domains found in other members of the phosphoglycerate mutase family, including a conserved histidine that is absolutely required for catalytic activity. However, this conserved domain is not sufficient for maximal phosphatase activity. We have identified a highly conserved amino acid motif, WDXNWD, located within the unique N-terminal region, which is required for assembly of PGAM5 into large multimeric complexes. Alanine substitutions wiThe Journal of biological chemistryA conserved motif mediates both multimer formation and allosteric activation of phosphoglycerate mutase 5.PMC4155678P50AT006273P50 AT006273Tipton PAHannink MWilkins JMMcConnell CfalseA conserved motif mediates both multimer formation and allosteric activation of phosphoglycerate mutase 5.Phosphoglycerate mutase 5 (PGAM5) is an atypical mitochondrial Ser/Thr phosphatase that modulates mitochondrial dynamics and participates in both apoptotic and necrotic cell death. The mechanisms that regulate the phosphatase activity of PGAM5 are poorly understood. The C-terminal phosphoglycerate mutase domain of PGAM5 shares homology with the catalytic domains found in other members of the phosphoglycerate mutase family, including a conserved histidine that is absolutely required for catalytic activity. However, this conserved domain is not sufficient for maximal phosphatase activity. We have identified a highly conserved amino acid motif, WDXNWD, located within the unique N-terminal region, which is required for assembly of PGAM5 into large multimeric complexes. Alanine substitutions wi2014-01-01T00:00:00Z2014 Sep2025-04-04T12:08:52.126Z2019-03-27T01:35:15ZS-EPMC41556782501265510.1074/jbc.M114.56554910.1074/jbc.m114.565549