1n95
From Proteopedia
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==Aryl Tetrahydrophyridine Inhbitors of Farnesyltranferase: Glycine, Phenylalanine and Histidine Derivatives== | ==Aryl Tetrahydrophyridine Inhbitors of Farnesyltranferase: Glycine, Phenylalanine and Histidine Derivatives== | ||
| - | <StructureSection load='1n95' size='340' side='right' caption='[[1n95]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='1n95' size='340' side='right'caption='[[1n95]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1n95]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1n95]] 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=1N95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N95 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTH:1-[2-(4-CYANO-BENZYLAMINO)-3-(3-METHYL-3H-IMIDAZOL-4-YL)-PROPIONYL]-5-NAPHTHALEN-1-YL-1,2,3,6-TETRAHYDRO-PYRIDINE-4-CARBONITRILE'>FTH</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]] 2.3Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FTH:1-[2-(4-CYANO-BENZYLAMINO)-3-(3-METHYL-3H-IMIDAZOL-4-YL)-PROPIONYL]-5-NAPHTHALEN-1-YL-1,2,3,6-TETRAHYDRO-PYRIDINE-4-CARBONITRILE'>FTH</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=1n95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n95 OCA], [https://pdbe.org/1n95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n95 RCSB], [https://www.ebi.ac.uk/pdbsum/1n95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n95 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]] | ||
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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=1n95 ConSurf]. | </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=1n95 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 a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. The design, synthesis, SAR and biological properties of these compounds will be discussed. | ||
| - | + | ==See Also== | |
| - | + | *[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Rattus norvegicus]] |
| - | [[Category: | + | [[Category: Cohen J]] |
| - | [[Category: Gu | + | [[Category: Gu WZ]] |
| - | [[Category: | + | [[Category: Gwaltney II SL]] |
| - | [[Category: | + | [[Category: Hasvold L]] |
| - | [[Category: Imade | + | [[Category: Imade H]] |
| - | [[Category: Li | + | [[Category: Li Q]] |
| - | [[Category: Nelson | + | [[Category: Nelson LT]] |
| - | [[Category: | + | [[Category: O'Conner SJ]] |
| - | [[Category: | + | [[Category: Sullivan GM]] |
| - | [[Category: | + | [[Category: Wang W]] |
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Current revision
Aryl Tetrahydrophyridine Inhbitors of Farnesyltranferase: Glycine, Phenylalanine and Histidine Derivatives
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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
