2bed: Difference between revisions

Revision as of 17:36, 21 February 2008

Structure of FPT bound to inhibitor SCH207736

OverviewOverview

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 StructureAbout this Structure

2BED is a Protein complex structure of sequences from Rattus norvegicus with , and as ligands. Active as Protein farnesyltransferase, with EC number 2.5.1.58 Full crystallographic information is available from OCA.

ReferenceReference

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

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 '''Structure of FPT bound to inhibitor SCH207736'''<br />
 ==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.
+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==
-BED is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN, FPP and 736 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Protein_farnesyltransferase Protein farnesyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.58 2.5.1.58] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BED OCA].
+BED is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FPP:'>FPP</scene> and <scene name='pdbligand=736:'>736</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Protein_farnesyltransferase Protein farnesyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.58 2.5.1.58] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BED OCA].
 ==Reference==
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 [[Category: ptase]]
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