View source for 4gts

==Engineered RabGGTase in complex with BMS analogue 16==
<StructureSection load='4gts' size='340' side='right' caption='[[4gts]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gts]] 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=4GTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GTS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7TP:5-{(3R)-3-(4-HYDROXYBENZYL)-4-[(4-METHOXYPHENYL)SULFONYL]-1-[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]-2,3,4,5-TETRAHYDRO-1H-1,4-BENZODIAZEPIN-7-YL}FURAN-2-CARBALDEHYDE'>7TP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[4gtm|4gtm]], [[4gto|4gto]], [[4gtp|4gtp]], [[4gtq|4gtq]], [[4gtr|4gtr]], [[4gtt|4gtt]], [[4gtv|4gtv]]</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=4gts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gts OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gts RCSB], [http://www.ebi.ac.uk/pdbsum/4gts PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Members of the Ras superfamily of small GTPases are frequently mutated in cancer. Therefore, inhibitors have been developed to address the acitivity of these GTPases by inhibiting their prenylating enzymes FTase, GGTase I, and RabGGTase. In contrast to FTase and GGTase I, only a handful of RabGGTase inhibitors have been developed. The most active RabGGTase inhibitor known until recently was an FTase inhibitor which hit RabGGTase as an off-target. We recently reported our efforts to tune the selectivity of these inhibitors toward RabGGTase. Here we describe an extended set of selective inhibitors. The requirements for selective RabGGTase inhibitors are described in detail, guided by multiple crystal structures. In order to relate in vitro and cellular activity, a high-throughput assay system to detect the attachment of [(3)H]geranylgeranyl groups to Rab was used. Selective RabGGTase inhibition allows the establishment of novel drug discovery programs aimed at the development of anticancer therapeutics.

Development of Selective, Potent RabGGTase Inhibitors.,Stigter EA, Guo Z, Bon RS, Wu YW, Choidas A, Wolf A, Menninger S, Waldmann H, Blankenfeldt W, Goody RS J Med Chem. 2012 Oct 11;55(19):8330-40. doi: 10.1021/jm300624s. Epub 2012 Oct 3. PMID:22963166<ref>PMID:22963166</ref>

From MEDLINE&reg;/PubMed&reg;, 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: Rattus norvegicus]]
[[Category: Blankenfeldt, W]]
[[Category: Bon, R S]]
[[Category: Goody, R S]]
[[Category: Guo, Z]]
[[Category: Stigter, E A]]
[[Category: Waldmann, H]]
[[Category: Inhibitor]]
[[Category: Protein prenylation]]
[[Category: Transferase-transferase inhibitor complex]]