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| | ==Crystal structure of the human TBC1D20 RabGAP domain== | | ==Crystal structure of the human TBC1D20 RabGAP domain== |
| - | <StructureSection load='4hl4' size='340' side='right' caption='[[4hl4]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4hl4' size='340' side='right'caption='[[4hl4]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hl4]] is a 1 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=4HL4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HL4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hl4]] is a 1 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=4HL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HL4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hlq|4hlq]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TBC1D20, C20orf140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hl4 OCA], [https://pdbe.org/4hl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hl4 RCSB], [https://www.ebi.ac.uk/pdbsum/4hl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hl4 ProSAT]</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=4hl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hl4 OCA], [http://pdbe.org/4hl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hl4 RCSB], [http://www.ebi.ac.uk/pdbsum/4hl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hl4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN]] Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN] Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN]] GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. | + | [https://www.uniprot.org/uniprot/TBC20_HUMAN TBC20_HUMAN] GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of RabGAPs is involved in many diseases. By combining X-ray structure analysis and time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail. A glutamine residue of Rab proteins (cis-glutamine) that is essential for intrinsic activity is less important in the GAP-activated reaction. During generation of the RabGAP.Rab:GTP complex, there is a rapid conformational change in which the cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also important for GAP catalysis. However, as in the case of Ras, a trans-arginine is also recruited to complete the active center during this conformational change. In contrast to the RasGAP mechanism, an accumulation of a state in which phosphate is bound is not observed, and bond breakage is the rate-limiting step. The movement of trans-glutamine and trans-arginine into the catalytic site and bond breakage during hydrolysis are monitored in real time. The combination of X-ray structure analysis and time-resolved FTIR spectroscopy provides detailed insight in the catalysis of human Rab GTPases.
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| - | | + | |
| - | Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail.,Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136<ref>PMID:23236136</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4hl4" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Gavriljuk, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Gazdag, E M]] | + | [[Category: Gavriljuk K]] |
| - | [[Category: Gerwert, K]] | + | [[Category: Gazdag EM]] |
| - | [[Category: Goody, R S]] | + | [[Category: Gerwert K]] |
| - | [[Category: Itzen, A]] | + | [[Category: Goody RS]] |
| - | [[Category: Koetting, C]] | + | [[Category: Itzen A]] |
| - | [[Category: Catalytic domain]]
| + | [[Category: Koetting C]] |
| - | [[Category: Fluoride]]
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| - | [[Category: Gtp hydrolase]]
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| - | [[Category: Gtpase-activating protein]]
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| - | [[Category: Hydrolase activator]]
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| - | [[Category: Rab gtp-binding protein]]
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| - | [[Category: Rab1b]]
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| - | [[Category: Rabgap]]
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| - | [[Category: Tbc]]
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