3NCA

X-ray structure of ketohexokinase in complex with a thieno pyridinol compound

Summary for 3NCA

• Entry DOI: 10.2210/pdb3nca/pdb
• Related: 3NBV 3NBW 3NC2 3NC9
• Descriptor: Ketohexokinase, SULFATE ION, thieno[3,2-b]pyridin-7-ol, ... (4 entities in total)
• Functional Keywords: ketohexokinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 68592.55

Authors

Abad, M.C.,Gibbs, A.C.,Spurlino, J.C. (deposition date: 2010-06-04, release date: 2010-12-22, Last modification date: 2023-09-06)

Primary citation

Gibbs, A.C.,Abad, M.C.,Zhang, X.,Tounge, B.A.,Lewandowski, F.A.,Struble, G.T.,Sun, W.,Sui, Z.,Kuo, L.C.
Electron density guided fragment-based lead discovery of ketohexokinase inhibitors.
J.Med.Chem., 53:7979-7991, 2010

PubMed Abstract: A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments to leadlike compounds. Applying electron density of fragments within the protein binding site as defined by X-ray crystallography, one can generate target specific leads without the use of affinity data. Our approach contrasts with most fragment-based drug design methodology where solution activity is a main design guide. Herein we describe the discovery of submicromolar ketohexokinase inhibitors with promising druglike properties.

PubMed: 21033679
DOI: 10.1021/jm100677s

Experimental method

X-RAY DIFFRACTION (2.602 Å)