Structural Study of Monomethyl Fumarate-Bound Human GAPDH.

ABSTRACT: 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 molecule is covalently linked to the catalytic Cys152 of human GAPDH, and inhibits the catalytic activity of the residue and dramatically reduces the enzymatic 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⁺

SUBMITTER: Park JB 

PROVIDER: S-EPMC6715340 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature