Park, Jun Bae; Park, Hayeong; Son, Jimin; Ha, Sang-Jun; Cho, Hyun-Soo published the artcile< Structural study of monomethyl fumarate-bound human GAPDH>, Electric Literature of 112-63-0, the main research area is monomethyl fumarate GAPDH nicotinamide; crystallography; glyceraldehyde-3-phosphate dehydrogenase; inhibitor; monomethyl fumarate.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a core enzyme of the aerobic glycolytic pathway with versatile functions and is associated with cancer development. Recently, Kornberg et al. published the detailed correlation between GAPDH and di- or monomethyl fumarate (DMF or MMF), which are well-known GAPDH antagonists in the immune system. As an extension, herein, we report the crystal structure of MMF-bound human GAPDH at 2.29 Å. The MMF mol. is covalently linked to the catalytic Cys152 of human GAPDH, and inhibits the catalytic activity of the residue and dramatically reduces the enzymic activity of GAPDH. Structural comparisons between NAD+-bound GAPDH and MMF-bound GAPDH revealed that the covalently linked MMF can block the binding of the NAD+ co-substrate due to steric hindrance of the nicotinamide portion of the NAD+ mol., illuminating the specific mechanism by which MMF inhibits GAPDH. Our data provide insights into GAPDH antagonist development for GAPDH-mediated disease treatment.
Molecules and Cells published new progress about Homo sapiens. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Electric Literature of 112-63-0.
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