6IQ6

Crystal structure of GAPDH

6IQ6 の概要

• エントリーDOI: 10.2210/pdb6iq6/pdb
• 分子名称: Glyceraldehyde-3-phosphate dehydrogenase, (2Z)-4-methoxy-4-oxobut-2-enoic acid (3 entities in total)
• 機能のキーワード: gapdh, inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 289443.84

構造登録者

Park, J.B.,Park, H.Y. (登録日: 2018-11-06, 公開日: 2019-08-28, 最終更新日: 2024-11-13)

主引用文献

Park, J.B.,Park, H.,Son, J.,Ha, S.J.,Cho, H.S.
Structural Study of Monomethyl Fumarate-Bound Human GAPDH.
Mol.Cells, 42:597-603, 2019

PubMed 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 NADbound GAPDH and MMF-bound GAPDH revealed that the covalently linked MMF can block the binding of the NAD cosubstrate due to steric hindrance of the nicotinamide portion of the NAD molecule, illuminating the specific mechanism by which MMF inhibits GAPDH. Our data provide insights into GAPDH antagonist development for GAPDH-mediated disease treatment.

PubMed: 31387164
DOI: 10.14348/molcells.2019.0114

実験手法

X-RAY DIFFRACTION (2.29 Å)