3O0T

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

3O0T の概要

• エントリーDOI: 10.2210/pdb3o0t/pdb
• 関連するPDBエントリー: 3MXO
• 分子名称: Serine/threonine-protein phosphatase PGAM5, mitochondrial, PHOSPHATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: structural genomics, structural genomics consortium, sgc, phosphoglycerate mutase family member 5, pgam5, bxlbv68, mgc5352 protein, serine/threonine phosphatase, mitochondrial protein, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion outer membrane ; Single-pass membrane protein : Q96HS1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47069.19

構造登録者

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) (登録日: 2010-07-20, 公開日: 2010-10-06, 最終更新日: 2024-05-22)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)