6ynh
GAPDH purified from the supernatant of HEK293F cells: crystal form 4 of 4GAPDH purified from the supernatant of HEK293F cells: crystal form 4 of 4
Structural highlights
FunctionG3P_HUMAN Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.[1] [2] [3] Publication Abstract from PubMedBackground: n-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyses the NAD (+)-dependent oxidative phosphorylation of n-glyceraldehyde-3-phosphate to 1,3-diphospho-n-glycerate and its reverse reaction in glycolysis and gluconeogenesis. Methods: Four distinct crystal structures of human n-Glyceraldehyde-3-phosphate dehydrogenase ( HsGAPDH) have been determined from protein purified from the supernatant of HEK293F human epithelial kidney cells. Results: X-ray crystallography and mass-spectrometry indicate that the catalytic cysteine of the protein ( HsGAPDH Cys152) is partially oxidised to cysteine S-sulfonic acid. The average occupancy for the Cys152-S-sulfonic acid modification over the 20 crystallographically independent copies of HsGAPDH across three of the crystal forms obtained is 0.31+/-0.17. Conclusions: The modification induces no significant structural changes on the tetrameric enzyme, and only makes aspecific contacts to surface residues in the active site, in keeping with the hypothesis that the oxidising conditions of the secreted mammalian cell expression system result in HsGAPDH catalytic cysteine S-sulfonic acid modification and irreversible inactivation of the enzyme. Partial catalytic Cys oxidation of human GAPDH to Cys-sulfonic acid.,Lia A, Dowle A, Taylor C, Santino A, Roversi P Wellcome Open Res. 2020 Aug 25;5:114. doi: 10.12688/wellcomeopenres.15893.2., eCollection 2020. PMID:32802964[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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