1sa4

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|PDB= 1sa4 |SIZE=350|CAPTION= <scene name='initialview01'>1sa4</scene>, resolution 2.10&Aring;
|PDB= 1sa4 |SIZE=350|CAPTION= <scene name='initialview01'>1sa4</scene>, resolution 2.10&Aring;
|SITE=
|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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|LIGAND= <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <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>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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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|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>
|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])
|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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|DOMAIN=
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|RELATEDENTRY=[[1d8d|1D8D]], [[1ft1|1FT1]], [[1jcq|1JCQ]], [[1jcr|1JCR]], [[1o5m|1O5M]], [[1ld8|1LD8]], [[1sa5|1SA5]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sa4 OCA], [http://www.ebi.ac.uk/pdbsum/1sa4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sa4 RCSB]</span>
}}
}}
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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: FPP]]
 
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[[Category: JAN]]
 
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[[Category: SUC]]
 
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[[Category: ZN]]
 
[[Category: caax]]
[[Category: caax]]
[[Category: cancer]]
[[Category: cancer]]
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[[Category: zarnestra]]
[[Category: zarnestra]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:02:25 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:39:18 2008''

Revision as of 20:39, 30 March 2008

Image:1sa4.gif


PDB ID 1sa4

Drag the structure with the mouse to rotate
, resolution 2.10Å
Ligands: , , ,
Gene: FNTA (Homo sapiens), FNTB (Homo sapiens)
Activity: Protein farnesyltransferase, with EC number 2.5.1.58
Related: 1D8D, 1FT1, 1JCQ, 1JCR, 1O5M, 1LD8, 1SA5


Resources: FirstGlance, OCA, PDBsum, RCSB
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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