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6fae

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The Sec7 domain of IQSEC2 (Brag1) in complex with the small GTPase Arf1

Structural highlights

6fae is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.35Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARF1_HUMAN GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles.

Publication Abstract from PubMed

The Ras superfamily of small GTPases are guanine nucleotide dependent switches essential for numerous cellular processes. Mutations or dysregulation of these proteins are associated with many diseases, but unsuccessful attempts to target the small GTPases directly have resulted in them being classed as 'undruggable'. The GTP dependent signaling of these proteins is controlled by their regulators; guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in the Rho and Rab subfamilies, guanine nucleotide dissociation inhibitors (GDIs). This review covers the recent small molecule and biologics strategies to target the small GTPases through their regulators. It seeks to critically re-evaluate recent chemical biology practice, such as the presence of PAINs motifs and the cell-based readout using compounds that are weakly potent or of unknown specificity. It highlights the vast scope of potential approaches for targeting the small GTPases in the future through their regulatory proteins.

Targeting the Small GTPase Superfamily through their Regulatory Proteins.,Gray JL, von Delft F, Brennan P Angew Chem Int Ed Engl. 2019 Mar 14. doi: 10.1002/anie.201900585. PMID:30869179^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gray JL, von Delft F, Brennan P. Targeting the Small GTPase Superfamily through their Regulatory Proteins. Angew Chem Int Ed Engl. 2019 Mar 14. doi: 10.1002/anie.201900585. PMID:30869179 doi:http://dx.doi.org/10.1002/anie.201900585

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fae"

@@ Line 3: / Line 3: @@
 <StructureSection load='6fae' size='340' side='right'caption='[[6fae]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6fae]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FAE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6fae]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FAE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.35&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IQSEC2, KIAA0522 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ARF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=6fae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fae OCA], [http://pdbe.org/6fae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fae RCSB], [http://www.ebi.ac.uk/pdbsum/6fae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fae 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=6fae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fae OCA], [https://pdbe.org/6fae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fae RCSB], [https://www.ebi.ac.uk/pdbsum/6fae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fae ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/IQEC2_HUMAN IQEC2_HUMAN]] Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome;X-linked non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/IQEC2_HUMAN IQEC2_HUMAN]] Is a guanine nucleotide exchange factor for the ARF GTP-binding proteins.<ref>PMID:26793055</ref>  [[http://www.uniprot.org/uniprot/ARF1_HUMAN ARF1_HUMAN]] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles.
+[https://www.uniprot.org/uniprot/ARF1_HUMAN ARF1_HUMAN] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Brennan, P]]
+[[Category: Brennan P]]
-[[Category: Delft, F von]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Fairhead M]]
-[[Category: Fairhead, M]]
+[[Category: Gray J]]
-[[Category: Gray, J]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Von Delft F]]
-[[Category: Gtpase gef]]
-[[Category: Hydrolase]]

6fae

From Proteopedia

Current revision

The Sec7 domain of IQSEC2 (Brag1) in complex with the small GTPase Arf1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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