2bed
From Proteopedia
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Structure of FPT bound to inhibitor SCH207736
Overview
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.
About this Structure
2BED is a Protein complex structure of sequences from Rattus norvegicus with ZN, FPP and 736 as ligands. Active as Protein farnesyltransferase, with EC number 2.5.1.58 Full crystallographic information is available from OCA.
Reference
Enhanced FTase activity achieved via piperazine interaction with catalytic zinc., Njoroge FG, Vibulbhan B, Pinto P, Strickland C, Bishop WR, Nomeir A, Girijavallabhan V, Bioorg Med Chem Lett. 2006 Feb 15;16(4):984-8. Epub 2005 Nov 16. PMID:16298128
Page seeded by OCA on Wed Nov 21 08:45:45 2007
Categories: Protein complex | Protein farnesyltransferase | Rattus norvegicus | Strickland, C | 736 | FPP | ZN | Drug design | Farnesyl | Fpt | Ptase
