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1mzc

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[[Image:1mzc.jpg|left|200px]]<br /><applet load="1mzc" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1mzc, resolution 2.00&Aring;" />
 
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'''Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a'''<br />
 
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==Overview==
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==Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a==
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A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex formed between one of these compounds and FTase has been determined by X-ray crystallography. These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal.
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<StructureSection load='1mzc' size='340' side='right'caption='[[1mzc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1mzc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MZC 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&#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=BNE:2-[3-(3-ETHYL-1-METHYL-2-OXO-AZEPAN-3-YL)-PHENOXY]-4-[1-AMINO-1-(1-METHYL-1H-IMIDIZOL-5-YL)-ETHYL]-BENZONITRILE'>BNE</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</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=1mzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mzc OCA], [https://pdbe.org/1mzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mzc RCSB], [https://www.ebi.ac.uk/pdbsum/1mzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mzc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FNTA_HUMAN FNTA_HUMAN] 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/mz/1mzc_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=1mzc ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1MZC 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=BNE:'>BNE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MZC OCA].
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*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents., deSolms SJ, Ciccarone TM, MacTough SC, Shaw AW, Buser CA, Ellis-Hutchings M, Fernandes C, Hamilton KA, Huber HE, Kohl NE, Lobell RB, Robinson RG, Tsou NN, Walsh ES, Graham SL, Beese LS, Taylor JS, J Med Chem. 2003 Jul 3;46(14):2973-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12825937 12825937]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Beese, L S.]]
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[[Category: Beese LS]]
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[[Category: Buser, C A.]]
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[[Category: Buser CA]]
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[[Category: Ciccarone, T M.]]
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[[Category: Ciccarone TM]]
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[[Category: Ellis-Hutchings, M.]]
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[[Category: Ellis-Hutchings M]]
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[[Category: Fernandes, C.]]
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[[Category: Fernandes C]]
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[[Category: Graham, S L.]]
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[[Category: Graham SL]]
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[[Category: Hamilton, K A.]]
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[[Category: Hamilton KA]]
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[[Category: Huber, H E.]]
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[[Category: Huber HE]]
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[[Category: Kohl, N E.]]
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[[Category: Kohl NE]]
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[[Category: Lobell, R B.]]
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[[Category: Lobell RB]]
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[[Category: MacTough, S C.]]
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[[Category: MacTough SC]]
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[[Category: Robinson, R G.]]
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[[Category: Robinson RG]]
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[[Category: Shaw, A W.]]
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[[Category: Shaw AW]]
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[[Category: Taylor, J S.]]
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[[Category: Taylor JS]]
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[[Category: Tsou, N N.]]
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[[Category: Tsou NN]]
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[[Category: Walsh, E S.]]
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[[Category: Walsh ES]]
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[[Category: deSolms, S J.]]
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[[Category: DeSolms SJ]]
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[[Category: BNE]]
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[[Category: FPP]]
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[[Category: SUC]]
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[[Category: ZN]]
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[[Category: alpha-alpha barrel]]
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[[Category: caax]]
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[[Category: fpp]]
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[[Category: ftase]]
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[[Category: inhibitor]]
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[[Category: pftase]]
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[[Category: ras]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:38 2008''
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Current revision

Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a

PDB ID 1mzc

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