1kzp

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(New page: 200px<br /><applet load="1kzp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kzp, resolution 2.10&Aring;" /> '''PROTEIN FARNESYLTRAN...)
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[[Image:1kzp.jpg|left|200px]]<br /><applet load="1kzp" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kzp, resolution 2.10&Aring;" />
 
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'''PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT'''<br />
 
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==Overview==
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==PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT==
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Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl, lipid group to numerous essential signal transduction proteins, including, members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their, transforming activity. FTase inhibitors are currently in clinical trials, for the treatment of cancer. Here we present a complete series of, structures representing the major steps along the reaction coordinate of, this enzyme. From these observations can be deduced the determinants of, substrate specificity and an unusual mechanism in which product release, requires binding of substrate, analogous to classically processive, enzymes. A structural model for the transition state consistent with, previous mechanistic studies was also constructed. The processive nature, of the reaction suggests the structural basis for the successive addition, of two prenyl groups to Rab proteins by the homologous enzyme, geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to, differ in their mechanism of inhibiting the enzyme.
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<StructureSection load='1kzp' size='340' side='right'caption='[[1kzp]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kzp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KZP FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=FAR:FARNESYL'>FAR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kzp OCA], [https://pdbe.org/1kzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kzp RCSB], [https://www.ebi.ac.uk/pdbsum/1kzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kzp ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FNTA_RAT FNTA_RAT] Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kz/1kzp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1kzp ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their transforming activity. FTase inhibitors are currently in clinical trials for the treatment of cancer. Here we present a complete series of structures representing the major steps along the reaction coordinate of this enzyme. From these observations can be deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed. The processive nature of the reaction suggests the structural basis for the successive addition of two prenyl groups to Rab proteins by the homologous enzyme geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme.
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==About this Structure==
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Reaction path of protein farnesyltransferase at atomic resolution.,Long SB, Casey PJ, Beese LS Nature. 2002 Oct 10;419(6907):645-50. PMID:12374986<ref>PMID:12374986</ref>
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1KZP 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, FAR and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KZP OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Reaction path of protein farnesyltransferase at atomic resolution., Long SB, Casey PJ, Beese LS, Nature. 2002 Oct 10;419(6907):645-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12374986 12374986]
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</div>
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[[Category: Protein complex]]
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<div class="pdbe-citations 1kzp" style="background-color:#fffaf0;"></div>
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[[Category: Rattus norvegicus]]
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[[Category: Squalene synthase]]
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[[Category: Beese, L.S.]]
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[[Category: Casey, P.J.]]
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[[Category: Long, S.B.]]
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[[Category: ACY]]
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[[Category: FAR]]
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[[Category: ZN]]
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[[Category: caax]]
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[[Category: farnesyl protein transferase]]
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[[Category: farnesyl transferase]]
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[[Category: farnesyltransferase]]
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[[Category: fpt]]
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[[Category: ft]]
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[[Category: ftase]]
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[[Category: pft]]
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[[Category: pftase]]
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[[Category: ras cancer]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:06:22 2007''
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==See Also==
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*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Beese LS]]
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[[Category: Casey PJ]]
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[[Category: Long SB]]

Current revision

PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYLATED K-RAS4B PEPTIDE PRODUCT

PDB ID 1kzp

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