7EPM

human LDHC complexed with NAD+ and ethylamino acetic acid

7EPM の概要

• エントリーDOI: 10.2210/pdb7epm/pdb
• 分子名称: L-lactate dehydrogenase C chain, 2-(ethylamino)-2-oxidanylidene-ethanoic acid, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: complex, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77482.38

構造登録者

Yu, Y.,Chen, Q. (登録日: 2021-04-27, 公開日: 2022-03-02, 最終更新日: 2023-11-29)

主引用文献

Tan, H.,Wang, H.,Ma, J.,Deng, H.,He, Q.,Chen, Q.,Zhang, Q.
Identification of human LDHC4 as a potential target for anticancer drug discovery.
Acta Pharm Sin B, 12:2348-2357, 2022

PubMed Abstract: One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human was significantly expressed in lung cancer tissues, overexpression of in mice could promote tumor growth, and knock-down of could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

PubMed: 35646544
DOI: 10.1016/j.apsb.2021.12.002

実験手法

X-RAY DIFFRACTION (3 Å)