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3hxb
From Proteopedia
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| - | + | ==Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 6)== | |
| - | + | <StructureSection load='3hxb' size='340' side='right' caption='[[3hxb]], [[Resolution|resolution]] 2.25Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3hxb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HXB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BD5:N-[(BENZYLOXY)CARBONYL]-D-TYROSYL-L-PHENYLALANYL-L-TYROSINE'>BD5</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hxc|3hxc]], [[3hxd|3hxd]], [[3hxe|3hxe]], [[3hxf|3hxf]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rabggta, Ggta ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), Rabggtb, Ggtb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_geranylgeranyltransferase_type_II Protein geranylgeranyltransferase type II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.60 2.5.1.60] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hxb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hxb RCSB], [http://www.ebi.ac.uk/pdbsum/3hxb PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == 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/hx/3hxb_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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Rab geranylgeranyl transferase (RabGGTase) catalyzes the attachment of geranylgeranyl isoprenoids to Rab guanine triphosphatases, which are key regulators in vesicular transport. Because geranylgeranylation is required for proper function and overexpression of Rabs has been observed in various cancers, RabGGTase may be a target for novel therapeutics. The development of selective inhibitors is, however, difficult because two related enzymes involved in other cellular processes exist in eukaryotes and because RabGGTase recognizes protein substrates indirectly, resulting in relaxed specificity. We report the synthesis of a peptidic library based on the farnesyl transferase inhibitor pepticinnamin E. Of 469 compounds investigated, several were identified as selective for RabGGTase with low micromolar IC(50) values. The compounds were not generally cytotoxic and inhibited Rab isoprenylation in COS-7 cells. Crystal structure analysis revealed that selective inhibitors interact with a tunnel unique to RabGGTase, implying that this structural motif is an attractive target for improved RabGGTase inhibitors. | ||
| - | + | Design, synthesis, and characterization of peptide-based rab geranylgeranyl transferase inhibitors.,Tan KT, Guiu-Rozas E, Bon RS, Guo Z, Delon C, Wetzel S, Arndt S, Alexandrov K, Waldmann H, Goody RS, Wu YW, Blankenfeldt W J Med Chem. 2009 Dec 24;52(24):8025-37. PMID:19894725<ref>PMID:19894725</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | |||
| + | ==See Also== | ||
| + | *[[Geranylgeranyl transferase|Geranylgeranyl transferase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Protein geranylgeranyltransferase type II]] | [[Category: Protein geranylgeranyltransferase type II]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Alexandrov, K | + | [[Category: Alexandrov, K]] |
| - | [[Category: Blankenfeldt, W | + | [[Category: Blankenfeldt, W]] |
| - | [[Category: Goody, R S | + | [[Category: Goody, R S]] |
| - | [[Category: Guo, Z | + | [[Category: Guo, Z]] |
| - | [[Category: Waldmann, H | + | [[Category: Waldmann, H]] |
[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
[[Category: Prenyltransferase]] | [[Category: Prenyltransferase]] | ||
[[Category: Protein prenylation inhibition]] | [[Category: Protein prenylation inhibition]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 06:27, 18 December 2014
Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 6)
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