3STH

Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Toxoplasma gondii

3STH の概要

• エントリーDOI: 10.2210/pdb3sth/pdb
• 分子名称: Glyceraldehyde-3-phosphate dehydrogenase, SODIUM ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: structural genomics, seattle structural genomics center for infectious disease, ssgcid, gapdh, g3pd, glycolysis, nad, nucleotide binding domain, oxidoreductase
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 159333.06

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID),Staker, B.L.,Edwards, T.E.,Sankaran, B. (登録日: 2011-07-10, 公開日: 2011-08-03, 最終更新日: 2023-09-13)

主引用文献

Dubey, R.,Staker, B.L.,Foe, I.T.,Bogyo, M.,Myler, P.J.,Ngo, H.M.,Gubbels, M.J.
Membrane skeletal association and post-translational allosteric regulation of Toxoplasma gondii GAPDH1.
Mol.Microbiol., 103:618-634, 2017

PubMed Abstract: When Toxoplasma gondii egresses from the host cell, glyceraldehyde-3-phosphate dehydrogenase 1 (GAPDH1), which is primary a glycolysis enzyme but actually a quintessential multifunctional protein, translocates to the unique cortical membrane skeleton. Here, we report the 2.25 Å resolution crystal structure of the GAPDH1 holoenzyme in a quaternary complex providing the basis for the molecular dissection of GAPDH1 structure-function relationships Knockdown of GAPDH1 expression and catalytic site disruption validate the essentiality of GAPDH1 in intracellular replication but we confirmed that glycolysis is not strictly essential. We identify, for the first time, S-loop phosphorylation as a novel, critical regulator of enzymatic activity that is consistent with the notion that the S-loop is critical for cofactor binding, allosteric activation and oligomerization. We show that neither enzymatic activity nor phosphorylation state correlate with the ability to translocate to the cortex. However, we demonstrate that association of GAPDH1 with the cortex is mediated by the N-terminus, likely palmitoylation. Overall, glycolysis and cortical translocation are functionally decoupled by post-translational modifications.

PubMed: 27859784
DOI: 10.1111/mmi.13577

実験手法

X-RAY DIFFRACTION (2.25 Å)