5HEX

Crystal Structure of Human Hexokinase 2 with cmpd 30, a 2-amino-6-benzenesulfonamide glucosamine

5HEX の概要

• エントリーDOI: 10.2210/pdb5hex/pdb
• 関連するPDBエントリー: 5HFU
• 分子名称: Hexokinase-2, 2-[(3-bromobenzene-1-carbonyl)amino]-6-{[(4-carboxy-5-methylfuran-2-yl)sulfonyl]amino}-2,6-dideoxy-alpha-D-glucopyranos e (3 entities in total)
• 機能のキーワード: inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 208402.40

構造登録者

Campobasso, N.,Zhao, B.,Smallwood, A. (登録日: 2016-01-06, 公開日: 2016-03-30, 最終更新日: 2024-03-06)

主引用文献

Lin, H.,Zeng, J.,Xie, R.,Schulz, M.J.,Tedesco, R.,Qu, J.,Erhard, K.F.,Mack, J.F.,Raha, K.,Rendina, A.R.,Szewczuk, L.M.,Kratz, P.M.,Jurewicz, A.J.,Cecconie, T.,Martens, S.,McDevitt, P.J.,Martin, J.D.,Chen, S.B.,Jiang, Y.,Nickels, L.,Schwartz, B.J.,Smallwood, A.,Zhao, B.,Campobasso, N.,Qian, Y.,Briand, J.,Rominger, C.M.,Oleykowski, C.,Hardwicke, M.A.,Luengo, J.I.
Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors.
Acs Med.Chem.Lett., 7:217-222, 2016

PubMed Abstract: A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound 1. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an "induced-fit" conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound 34 with greater than 100-fold selectivity over HK1. Compound 25 inhibits in situ glycolysis in a UM-UC-3 bladder tumor cell line via (13)CNMR measurement of [3-(13)C]lactate produced from [1,6-(13)C2]glucose added to the cell culture.

PubMed: 26985301
DOI: 10.1021/acsmedchemlett.5b00214

実験手法

X-RAY DIFFRACTION (2.734 Å)