2BED

Structure of FPT bound to inhibitor SCH207736

Summary for 2BED

• Entry DOI: 10.2210/pdb2bed/pdb
• Descriptor: Protein farnesyltransferase/geranylgeranyltransferase type I alpha subunit, Protein farnesyltransferase beta subunit, ZINC ION, ... (6 entities in total)
• Functional Keywords: fpt, ptase, farnesyl, drug design, transferase
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 2
• Total formula weight: 83491.41

Authors

Strickland, C. (deposition date: 2005-10-24, release date: 2006-08-08, Last modification date: 2024-02-14)

Primary citation

Njoroge, F.G.,Vibulbhan, B.,Pinto, P.,Strickland, C.,Bishop, W.R.,Nomeir, A.,Girijavallabhan, V.
Enhanced FTase activity achieved via piperazine interaction with catalytic zinc.
Bioorg.Med.Chem.Lett., 16:984-988, 2006

PubMed Abstract: Benzocycloheptapyridine tricyclic compounds with piperazine or substituted piperidine moieties extending either from the 5- or 6-position of the tricyclic bridgehead exhibited enhanced FTase activity: this resulted from favorable binding of the ligand nitrogen with the catalytic zinc found in the FTase. A single isomer at C-11 with piperazine adduct extending from the 6-position, compound 24, exhibited excellent FTase activity with IC50 = 0.007 microM, soft agar IC50 = 72 nM, and Rat AUC(PO, 10 mpk) = 4.0 microM x h. X-ray of (-)-[8-chloro-6-(1-piperazinyl)-1H-benzo[5,6]]cyclohepta[1,2-b]pyridine-11-yl]-1-(methylsulfonyl)piperidine 24 bound to Ftase revealed favorable interaction between piperazine nitrogen and catalytic zinc atom.

PubMed: 16298128
DOI: 10.1016/j.bmcl.2005.10.090

Experimental method

X-RAY DIFFRACTION (2.7 Å)