3ASX

Human Squalene synthase in complex with 1-{4-[{4-chloro-2-[(2-chlorophenyl)(hydroxy)methyl]phenyl}(2,2-dimethylpropyl)amino]-4-oxobutanoyl}piperidine-3-carboxylic acid

Summary for 3ASX

• Entry DOI: 10.2210/pdb3asx/pdb
• Related: 3Q2Z 3Q30
• Descriptor: Squalene synthase, PHOSPHATE ION, (3R)-1-{4-[{4-chloro-2-[(S)-(2-chlorophenyl)(hydroxy)methyl]phenyl}(2,2-dimethylpropyl)amino]-4-oxobutanoyl}piperidine-3-carboxylic acid, ... (4 entities in total)
• Functional Keywords: isoprene biosynthesis, lipid synthesis, multifunctional enzyme, oxidoreductase, steroid biosynthesis, sterol biosynthesis, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P37268
• Total number of polymer chains: 1
• Total formula weight: 39811.16

Authors

Shimizu, H.,Suzuki, M.,Katakura, S.,Yamazaki, K.,Higashihashi, N.,Ichikawa, M.,Yokomizo, A.,Itoh, M.,Sugita, K.,Usui, H. (deposition date: 2010-12-22, release date: 2011-12-21, Last modification date: 2023-11-01)

Primary citation

Ichikawa, M.,Yokomizo, A.,Itoh, M.,Sugita, K.,Usui, H.,Shimizu, H.,Suzuki, M.,Terayama, K.,Kanda, A.
Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors
Bioorg.Med.Chem., 19:1930-1949, 2011

PubMed Abstract: To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds. Further chemical modification led to the discovery of a novel template with a strong squalene synthase inhibitory activity, and its basic structure-activity relationship was revealed. The X-ray crystallographic data of compound 12 bound to the active site of squalene synthase provided an important insight into the binding mode of this alternative template that formed 11-membered ring conformations with an intramolecular hydrogen bond.

PubMed: 21353782
DOI: 10.1016/j.bmc.2011.01.065

Experimental method

X-RAY DIFFRACTION (2 Å)