6SBU

X-ray Structure of Human LDHA with an Allosteric Inhibitor (Compound 3)

6SBU の概要

• エントリーDOI: 10.2210/pdb6sbu/pdb
• 分子名称: L-lactate dehydrogenase A chain, 4-[[4-[(5-chloranylthiophen-2-yl)carbonylamino]-1,3-bis(oxidanylidene)isoindol-2-yl]methyl]benzoic acid, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: ldha, oxidoreductase, oxidoreductase inhibitor, allosteric inhibitor
• 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: 298141.95

構造登録者

Friberg, A.,Puetter, V.,Nguyen, D.,Rehwinkel, H. (登録日: 2019-07-22, 公開日: 2020-06-10, 最終更新日: 2024-01-24)

主引用文献

Friberg, A.,Rehwinkel, H.,Nguyen, D.,Putter, V.,Quanz, M.,Weiske, J.,Eberspacher, U.,Heisler, I.,Langer, G.
Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.
Acs Omega, 5:13034-13041, 2020

PubMed Abstract: Lactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer.

PubMed: 32548488
DOI: 10.1021/acsomega.0c00715

実験手法

X-RAY DIFFRACTION (2.91 Å)