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3hxe

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Revision as of 05:11, 16 November 2017

Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 37)

Structural highlights

3hxe is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3hxb, 3hxc, 3hxd, 3hxf
Activity:	Protein geranylgeranyltransferase type II, with EC number 2.5.1.60
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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. [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.

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hxe"

@@ Line 1: / Line 1: @@
 ==Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 37)==
 <StructureSection load='3hxe' size='340' side='right' caption='[[3hxe]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hxb|3hxb]], [[3hxc|3hxc]], [[3hxd|3hxd]], [[3hxf|3hxf]]</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]</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>
 </table>
 == Function ==
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 3hxe" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Geranylgeranyl transferase|Geranylgeranyl transferase]]
 == References ==
 <references/>

3hxe

From Proteopedia

Revision as of 05:11, 16 November 2017

Engineered RabGGTase in complex with a peptidomimetic inhibitor (compound 37)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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