2bed: Difference between revisions

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Revision as of 17:00, 20 March 2008

File:2bed.gif

, resolution 2.700Å

Ligands:

, and

Gene:

Fnta (Rattus norvegicus), Fntb (Rattus norvegicus)

Activity:

Protein farnesyltransferase, with EC number 2.5.1.58

Coordinates:

save as pdb, mmCIF, xml

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. 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

Page seeded by OCA on Thu Mar 20 16:00:51 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2bed.gif|left|200px]]<br /><applet load="2bed" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2bed.gif|left|200px]]
-caption="2bed, resolution 2.700&Aring;" />
-'''Structure of FPT bound to inhibitor SCH207736'''<br />
+ {{Structure
+|PDB= 2bed |SIZE=350|CAPTION= <scene name='initialview01'>2bed</scene>, resolution 2.700&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene> and <scene name='pdbligand=736:(11S)-8-CHLORO-11-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]-6-PIPERAZIN-1-YL-11H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDINE'>736</scene>
+|ACTIVITY= [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]
+|GENE= Fnta ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), Fntb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
+}}
+'''Structure of FPT bound to inhibitor SCH207736'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==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 <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].
+BED is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BED 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16298128 16298128]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/16298128 16298128]
 [[Category: Protein complex]]
 [[Category: Protein farnesyltransferase]]
@@ Line 23: / Line 32: @@
 [[Category: ptase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:36:54 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:00:51 2008''