3O0T

Crystal structure of human phosphoglycerate mutase family member 5 (PGAM5) in complex with phosphate

Summary for 3O0T

• Entry DOI: 10.2210/pdb3o0t/pdb
• Related: 3MXO
• Descriptor: Serine/threonine-protein phosphatase PGAM5, mitochondrial, PHOSPHATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: structural genomics, structural genomics consortium, sgc, phosphoglycerate mutase family member 5, pgam5, bxlbv68, mgc5352 protein, serine/threonine phosphatase, mitochondrial protein, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion outer membrane ; Single-pass membrane protein : Q96HS1
• Total number of polymer chains: 2
• Total formula weight: 47069.19

Authors

Chaikuad, A.,Alfano, I.,Picaud, S.,Filippakopoulos, P.,Barr, A.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Takeda, K.,Ichijo, H.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2010-07-20, release date: 2010-10-06, Last modification date: 2024-05-22)

Primary citation

Chaikuad, A.,Filippakopoulos, P.,Marcsisin, S.R.,Picaud, S.,Schroder, M.,Sekine, S.,Ichijo, H.,Engen, J.R.,Takeda, K.,Knapp, S.
Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly.
Structure, 25:1089-1099.e3, 2017

PubMed Abstract: PGAM5 is a mitochondrial membrane protein that functions as an atypical Ser/Thr phosphatase and is a regulator of oxidative stress response, necroptosis, and autophagy. Here we present several crystal structures of PGAM5 including the activating N-terminal regulatory sequences, providing a model for structural plasticity, dimerization of the catalytic domain, and the assembly into an enzymatically active dodecameric form. Oligomeric states observed in structures were supported by hydrogen exchange mass spectrometry, size-exclusion chromatography, and analytical ultracentrifugation experiments in solution. We report that the catalytically important N-terminal WDPNWD motif acts as a structural integrator assembling PGAM5 into a dodecamer, allosterically activating the phosphatase by promoting an ordering of the catalytic loop. Additionally the observed active site plasticity enabled visualization of essential conformational rearrangements of catalytic elements. The comprehensive biophysical characterization offers detailed structural models of this key mitochondrial phosphatase that has been associated with the development of diverse diseases.

PubMed: 28648608
DOI: 10.1016/j.str.2017.05.020

Experimental method

X-RAY DIFFRACTION (1.9 Å)