5HG1

Crystal Structure of Human Hexokinase 2 with cmpd 1, a C-2-substituted glucosamine

Summary for 5HG1

• Entry DOI: 10.2210/pdb5hg1/pdb
• Related: 5HEX 5HFU
• Descriptor: Hexokinase-2, 2-deoxy-2-{[(2E)-3-(3,4-dichlorophenyl)prop-2-enoyl]amino}-alpha-D-glucopyranose, 6-O-phosphono-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: metabolism, inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 104150.96

Authors

Campobasso, N.,Zhao, B.,Smallwood, A. (deposition date: 2016-01-07, release date: 2016-03-30, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.76 Å)