5V4X

Human glucokinase in complex with novel pyrazole activator.

Summary for 5V4X

Entry DOI	10.2210/pdb5v4x/pdb
Related	5V4W
Descriptor	Glucokinase, alpha-D-glucopyranose, (2S)-3-cyclohexyl-2-[4-(cyclopentylsulfonyl)-2-oxopyridin-1(2H)-yl]-N-(1,3-thiazol-2-yl)propanamide, ... (5 entities in total)
Functional Keywords	activator, complex, glucokinase, transferase-transferase activator complex, transferase/transferase activator
Biological source	Homo sapiens (Human)
Total number of polymer chains	1
Total formula weight	52417.01
Authors	Skene, R.J.,Hosfiled, D.J. (deposition date: 2017-03-10, release date: 2017-05-31, Last modification date: 2024-03-06)
Primary citation	Cheruvallath, Z.S.,Gwaltney, S.L.,Sabat, M.,Tang, M.,Wang, H.,Jennings, A.,Hosfield, D.,Lee, B.,Wu, Y.,Halkowycz, P.,Grimshaw, C.E. Discovery of potent and orally active 1,4-disubstituted indazoles as novel allosteric glucokinase activators. Bioorg. Med. Chem. Lett., 27:2678-2682, 2017 Cited by PubMed Abstract: Guided by co-crystal structural information obtained from a different series we were exploring, a scaffold morphing and SBDD approach led to the discovery of the 1,4-disubstituted indazole series as a novel class of GKAs that potently activate GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated with 29 in a rodent models of type 2 diabetes. PubMed: 28512030 DOI: 10.1016/j.bmcl.2017.04.041 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (2.08 Å)

Structure validation