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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 597 - 603 (7page)
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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+ 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.
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참고문헌 (31)
참고문헌 신청
Ahuja, M. / 2016 / Distinct Nrf2 signaling mechanisms of fumaric acid esters and their role in neuroprotection against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced experimental Parkinson’s-like disease / J. Neurosci 36:6332~6351
Araki, K. / 2007 / Hepatocellular carcinoma producing a granulocyte colony-stimulating factor : report of a resected case with a literature review / Liver Int 27:716~721
Blair, H. A. / 2018 / Dimethyl fumarate : a review in moderate to severe plaque psoriasis / Drugs 78:123~130
Bomprezzi, R. / 2015 / Dimethyl fumarate in the treatment of relapsingremitting multiple sclerosis : an overview / Ther. Adv. Neurol. Disord 8:20~30
Colell, A. / 2009 / Novel roles for GAPDH in cell death and carcinogenesis / Cell Death Differ 16:1573~1581
Araki, K. / 2007 / Hepatocellular carcinoma producing a granulocyte colony-stimulating factor : report of a resected case with a literature review / Liver Int 27:716~721
Blair, H. A. / 2018 / Dimethyl fumarate : a review in moderate to severe plaque psoriasis / Drugs 78:123~130
Bomprezzi, R. / 2015 / Dimethyl fumarate in the treatment of relapsingremitting multiple sclerosis : an overview / Ther. Adv. Neurol. Disord 8:20~30
Colell, A. / 2009 / Novel roles for GAPDH in cell death and carcinogenesis / Cell Death Differ 16:1573~1581
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