1sa5

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[[Image:1sa5.gif|left|200px]]
[[Image:1sa5.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1sa5 |SIZE=350|CAPTION= <scene name='initialview01'>1sa5</scene>, resolution 2.60&Aring;
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The line below this paragraph, containing "STRUCTURE_1sa5", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=BMV:3-BENZYL-1-(1H-IMIDAZOL-4-YLMETHYL)-4-(THIEN-2-YLSULFONYL)-2,3,4,5-TETRAHYDRO-1H-1,4-BENZODIAZEPINE-7-CARBONITRILE'>BMV</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|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])
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-->
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|DOMAIN=
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{{STRUCTURE_1sa5| PDB=1sa5 | SCENE= }}
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|RELATEDENTRY=[[1d8d|1D8D]], [[1ft1|1FT1]], [[1jcq|1JCQ]], [[1jcr|1JCR]], [[1ld8|1LD8]], [[1o5m|1O5M]], [[1sa4|1SA4]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sa5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sa5 OCA], [http://www.ebi.ac.uk/pdbsum/1sa5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sa5 RCSB]</span>
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}}
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'''Rat protein farnesyltransferase complexed with FPP and BMS-214662'''
'''Rat protein farnesyltransferase complexed with FPP and BMS-214662'''
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[[Category: Beese, L S.]]
[[Category: Beese, L S.]]
[[Category: Reid, T S.]]
[[Category: Reid, T S.]]
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[[Category: bms-214662]]
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[[Category: Bms-214662]]
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[[Category: caax]]
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[[Category: Caax]]
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[[Category: cancer]]
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[[Category: Cancer]]
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[[Category: clinical candidate]]
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[[Category: Clinical candidate]]
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[[Category: farnesyl transferase]]
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[[Category: Farnesyl transferase]]
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[[Category: farnesyltransferase]]
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[[Category: Farnesyltransferase]]
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[[Category: ftase]]
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[[Category: Ftase]]
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[[Category: fti]]
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[[Category: Fti]]
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[[Category: inhibitor]]
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[[Category: Inhibitor]]
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[[Category: lipid modification]]
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[[Category: Lipid modification]]
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[[Category: protein prenylation]]
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[[Category: Protein prenylation]]
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[[Category: ra]]
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[[Category: Ra]]
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[[Category: tumor regression]]
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[[Category: Tumor regression]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:28:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:39:23 2008''
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Revision as of 05:28, 3 May 2008

Image:1sa5.gif

Template:STRUCTURE 1sa5

Rat protein farnesyltransferase complexed with FPP and BMS-214662


Overview

The search for new cancer therapeutics has identified protein farnesyltransferase (FTase) as a promising drug target. This enzyme attaches isoprenoid lipids to signal transduction proteins involved in growth and differentiation. The two FTase inhibitors (FTIs), R115777 (tipifarnib/Zarnestra) and BMS-214662, have undergone evaluation as cancer therapeutics in phase I and II clinical trials. R115777 has been evaluated in phase III clinical trials and shows indications for the treatment of blood and breast malignancies. Here we present crystal structures of R115777 and BMS-214662 complexed with mammalian FTase. These structures illustrate the molecular mechanism of inhibition and selectivity toward FTase over the related enzyme, protein geranylgeranyltransferase type I (GGTase-I). These results, combined with previous biochemical and structural analyses, identify features of FTase that could be exploited to modulate inhibitor potency and specificity and should aid in the continued development of FTIs as therapeutics for the treatment of cancer and parasitic infections.

About this Structure

1SA5 is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity., Reid TS, Beese LS, Biochemistry. 2004 Jun 8;43(22):6877-84. PMID:15170324 Page seeded by OCA on Sat May 3 08:28:36 2008

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