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New page: left|200px<br /> <applet load="1mzc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mzc, resolution 2.00Å" /> '''Co-Crystal Structur...
 
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[[Image:1mzc.gif|left|200px]]<br />
<applet load="1mzc" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1mzc, resolution 2.00&Aring;" />
'''Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a'''<br />


==Overview==
==Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a==
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.
<StructureSection load='1mzc' size='340' side='right'caption='[[1mzc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Function ==
[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).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mz/1mzc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>


==About this Structure==
==See Also==
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 SUC, ZN, FPP and BNE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MZC OCA].
*[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Beese, L.S.]]
[[Category: Beese LS]]
[[Category: Buser, C.A.]]
[[Category: Buser CA]]
[[Category: Ciccarone, T.M.]]
[[Category: Ciccarone TM]]
[[Category: Ellis-Hutchings, M.]]
[[Category: Ellis-Hutchings M]]
[[Category: Fernandes, C.]]
[[Category: Fernandes C]]
[[Category: Graham, S.L.]]
[[Category: Graham SL]]
[[Category: Hamilton, K.A.]]
[[Category: Hamilton KA]]
[[Category: Huber, H.E.]]
[[Category: Huber HE]]
[[Category: Kohl, N.E.]]
[[Category: Kohl NE]]
[[Category: Lobell, R.B.]]
[[Category: Lobell RB]]
[[Category: MacTough, S.C.]]
[[Category: MacTough SC]]
[[Category: Robinson, R.G.]]
[[Category: Robinson RG]]
[[Category: Shaw, A.W.]]
[[Category: Shaw AW]]
[[Category: Taylor, J.S.]]
[[Category: Taylor JS]]
[[Category: Tsou, N.N.]]
[[Category: Tsou NN]]
[[Category: Walsh, E.S.]]
[[Category: Walsh ES]]
[[Category: deSolms, S.J.]]
[[Category: DeSolms SJ]]
[[Category: BNE]]
[[Category: FPP]]
[[Category: SUC]]
[[Category: ZN]]
[[Category: alpha-alpha barrel]]
[[Category: caax]]
[[Category: fpp]]
[[Category: ftase]]
[[Category: inhibitor]]
[[Category: pftase]]
[[Category: ras]]
 
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