1sa4

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[[Image:1sa4.gif|left|200px]]<br /><applet load="1sa4" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1sa4.gif|left|200px]]
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caption="1sa4, resolution 2.10&Aring;" />
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'''human protein farnesyltransferase complexed with FPP and R115777'''<br />
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{{Structure
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|PDB= 1sa4 |SIZE=350|CAPTION= <scene name='initialview01'>1sa4</scene>, resolution 2.10&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene> and <scene name='pdbligand=JAN:6-[(S)-AMINO(4-CHLOROPHENYL)(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]-4-(3-CHLOROPHENYL)-1-METHYLQUINOLIN-2(1H)-ONE'>JAN</scene>
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|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]
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|GENE= FNTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), FNTB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''human protein farnesyltransferase complexed with FPP and R115777'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1SA4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FPP:'>FPP</scene> and <scene name='pdbligand=JAN:'>JAN</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=1SA4 OCA].
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1SA4 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SA4 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15170324 15170324]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15170324 15170324]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: protein prenylation]]
[[Category: protein prenylation]]
[[Category: r115777]]
[[Category: r115777]]
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[[Category: ras]]
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[[Category: ra]]
[[Category: tipifarnib]]
[[Category: tipifarnib]]
[[Category: tumor regression]]
[[Category: tumor regression]]
[[Category: zarnestra]]
[[Category: zarnestra]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:02:25 2008''

Revision as of 12:02, 20 March 2008

Image:1sa4.gif


PDB ID 1sa4

Drag the structure with the mouse to rotate
, resolution 2.10Å
Ligands: , , and
Gene: FNTA (Homo sapiens), FNTB (Homo sapiens)
Activity: Protein farnesyltransferase, with EC number 2.5.1.58
Coordinates: save as pdb, mmCIF, xml



human protein farnesyltransferase complexed with FPP and R115777


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

1SA4 is a Protein complex structure of sequences from Homo sapiens. 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

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