1n9a
From Proteopedia
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==Farnesyltransferase complex with tetrahydropyridine inhibitors== | ==Farnesyltransferase complex with tetrahydropyridine inhibitors== | ||
| - | <StructureSection load='1n9a' size='340' side='right' caption='[[1n9a]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='1n9a' size='340' side='right'caption='[[1n9a]], [[Resolution|resolution]] 3.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1n9a]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1n9a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N9A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTI:1-{2-[3-(4-CYANO-BENZYL)-3H-IMIDAZOL-4-YL]-ACETYL}-5-NAPHTHALEN-1-YL-1,2,3,6-TETRAHYDRO-PYRIDINE-4-CARBONITRILE'>FTI</scene>, <scene name='pdbligand=HFP:ALPHA-HYDROXYFARNESYLPHOSPHONIC+ACID'>HFP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FTI:1-{2-[3-(4-CYANO-BENZYL)-3H-IMIDAZOL-4-YL]-ACETYL}-5-NAPHTHALEN-1-YL-1,2,3,6-TETRAHYDRO-PYRIDINE-4-CARBONITRILE'>FTI</scene>, <scene name='pdbligand=HFP:ALPHA-HYDROXYFARNESYLPHOSPHONIC+ACID'>HFP</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'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n9a OCA], [https://pdbe.org/1n9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n9a RCSB], [https://www.ebi.ac.uk/pdbsum/1n9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n9a ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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). |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n9/1n9a_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n9/1n9a_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=1n9a ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered bioavailable aryl tetrahydropyridines that are potent in cell culture. The design, synthesis, SAR and biological properties of these compounds will be discussed. | ||
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| - | Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency.,Gwaltney SL 2nd, O'Connor SJ, Nelson LT, Sullivan GM, Imade H, Wang W, Hasvold L, Li Q, Cohen J, Gu WZ, Tahir SK, Bauch J, Marsh K, Ng SC, Frost DJ, Zhang H, Muchmore S, Jakob CG, Stoll V, Hutchins C, Rosenberg SH, Sham HL Bioorg Med Chem Lett. 2003 Apr 7;13(7):1363-6. PMID:12657283<ref>PMID:12657283</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
==See Also== | ==See Also== | ||
| - | *[[Farnesyltransferase|Farnesyltransferase]] | + | *[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]] |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Cohen | + | [[Category: Cohen J]] |
| - | [[Category: | + | [[Category: Gu WZ]] |
| - | [[Category: | + | [[Category: Gwaltney II SL]] |
| - | [[Category: Hasvold | + | [[Category: Hasvold L]] |
| - | + | [[Category: Imade H]] | |
| - | [[Category: Imade | + | [[Category: Li Q]] |
| - | [[Category: Li | + | [[Category: Nelson LT]] |
| - | [[Category: Nelson | + | [[Category: O'Conner SJ]] |
| - | [[Category: | + | [[Category: Sullivan GM]] |
| - | [[Category: | + | [[Category: Wang W]] |
| - | [[Category: | + | |
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Current revision
Farnesyltransferase complex with tetrahydropyridine inhibitors
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Categories: Large Structures | Rattus norvegicus | Cohen J | Gu WZ | Gwaltney II SL | Hasvold L | Imade H | Li Q | Nelson LT | O'Conner SJ | Sullivan GM | Wang W
