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| | <StructureSection load='3hxb' size='340' side='right'caption='[[3hxb]], [[Resolution|resolution]] 2.25Å' scene=''> | | <StructureSection load='3hxb' size='340' side='right'caption='[[3hxb]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3hxb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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 [https://proteopedia.org/fgij/fg.htm?mol=3HXB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3hxb]] 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=3HXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HXB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hxc|3hxc]], [[3hxd|3hxd]], [[3hxe|3hxe]], [[3hxf|3hxf]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rabggta, Ggta ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Rabggtb, Ggtb ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein_geranylgeranyltransferase_type_II Protein geranylgeranyltransferase type II], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3hxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hxb OCA], [https://pdbe.org/3hxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hxb RCSB], [https://www.ebi.ac.uk/pdbsum/3hxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hxb ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hxb OCA], [https://pdbe.org/3hxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hxb RCSB], [https://www.ebi.ac.uk/pdbsum/3hxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hxb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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. [[https://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.
| + | [https://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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein geranylgeranyltransferase type II]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Alexandrov, K]] | + | [[Category: Alexandrov K]] |
| - | [[Category: Blankenfeldt, W]] | + | [[Category: Blankenfeldt W]] |
| - | [[Category: Goody, R S]] | + | [[Category: Goody RS]] |
| - | [[Category: Guo, Z]] | + | [[Category: Guo Z]] |
| - | [[Category: Waldmann, H]] | + | [[Category: Waldmann H]] |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Prenyltransferase]]
| + | |
| - | [[Category: Protein prenylation inhibition]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
Function
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Design, synthesis, and characterization of peptide-based rab geranylgeranyl transferase inhibitors. J Med Chem. 2009 Dec 24;52(24):8025-37. PMID:19894725 doi:10.1021/jm901117d
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