5KRE

Covalent inhibitor of LYPLAL1

5KRE の概要

• エントリーDOI: 10.2210/pdb5kre/pdb
• 分子名称: Lysophospholipase-like protein 1, (2~{R})-2-phenylpiperidine-1-carbaldehyde, NITRATE ION, ... (4 entities in total)
• 機能のキーワード: lyplal1, serine hydrolase, covalent inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Cytoplasm, cytosol . Isoform 2: Cytoplasm, cytosol : Q5VWZ2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26772.90

構造登録者

Pandit, J. (登録日: 2016-07-07, 公開日: 2016-07-20, 最終更新日: 2024-11-06)

主引用文献

Ahn, K.,Boehm, M.,Brown, M.F.,Calloway, J.,Che, Y.,Chen, J.,Fennell, K.F.,Geoghegan, K.F.,Gilbert, A.M.,Gutierrez, J.A.,Kalgutkar, A.S.,Lanba, A.,Limberakis, C.,Magee, T.V.,O'Doherty, I.,Oliver, R.,Pabst, B.,Pandit, J.,Parris, K.,Pfefferkorn, J.A.,Rolph, T.P.,Patel, R.,Schuff, B.,Shanmugasundaram, V.,Starr, J.T.,Varghese, A.H.,Vera, N.B.,Vernochet, C.,Yan, J.
Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism.
Acs Chem.Biol., 11:2529-2540, 2016

PubMed Abstract: Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization.

PubMed: 27391855
DOI: 10.1021/acschembio.6b00266

実験手法

X-RAY DIFFRACTION (2 Å)