3hxe

<StructureSection load='3hxe' size='340' side='right' caption='[[3hxe]], [[Resolution|resolution]] 1.95&Aring;' scene=''>

<table><tr><td colspan='2'>[[3hxe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HXE FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BD8:N-UNDECANOYL-L-HISTIDYL-L-PHENYLALANYL-N-METHYL-N-(2-PYRIDIN-2-YLETHYL)-L-TYROSINAMIDE'>BD8</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3hxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hxe OCA], [http://pdbe.org/3hxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hxe RCSB], [http://www.ebi.ac.uk/pdbsum/3hxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hxe ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/PGTA_RAT PGTA_RAT]] Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to both cysteines in Rab proteins with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A and RAB5A respectively. [[http://www.uniprot.org/uniprot/PGTB2_RAT PGTB2_RAT]] Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to both cysteines in Rab proteins with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A and RAB5A respectively.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hx/3hxe_consurf.spt"</scriptWhenChecked>

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== 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.

 

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== References ==

[[Category: Buffalo rat]]

[[Category: Protein geranylgeranyltransferase type II]]

[[Category: Alexandrov, K]]

[[Category: Blankenfeldt, W]]

[[Category: Goody, R S]]

[[Category: Guo, Z]]

[[Category: Waldmann, H]]

[[Category: Transferase]]