3KC0

Crystal structure of human liver FBPase in complex with tricyclic inhibitor 10b

Summary for 3KC0

• Entry DOI: 10.2210/pdb3kc0/pdb
• Related: 3KBZ 3KC1
• Descriptor: Fructose-1,6-bisphosphatase 1, [(8H-indeno[1,2-d][1,3]thiazol-4-yloxy)methyl]phosphonic acid (3 entities in total)
• Functional Keywords: hydrolase, allosteric enzyme, carbohydrate metabolism, disease mutation, gluconeogenesis, magnesium, metal-binding, polymorphism
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 148045.87

Authors

Takahashi, M.,Sone, J.,Hanzawa, H. (deposition date: 2009-10-20, release date: 2010-02-02, Last modification date: 2023-11-01)

Primary citation

Tsukada, T.,Takahashi, M.,Takemoto, T.,Kanno, O.,Yamane, T.,Kawamura, S.,Nishi, T.
Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors.
Bioorg.Med.Chem.Lett., 20:1004-1007, 2010

PubMed Abstract: With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.

PubMed: 20045638
DOI: 10.1016/j.bmcl.2009.12.056

Experimental method

X-RAY DIFFRACTION (2.8 Å)