|
|
| Line 1: |
Line 1: |
| | | | |
| | ==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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hlq|4hlq]]</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='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'>[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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 24: |
| | __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]]
| + | |
| - | [[Category: Gtp hydrolase]]
| + | |
| - | [[Category: Gtpase-activating protein]]
| + | |
| - | [[Category: Hydrolase activator]]
| + | |
| - | [[Category: Rab gtp-binding protein]]
| + | |
| - | [[Category: Rab1b]]
| + | |
| - | [[Category: Rabgap]]
| + | |
| - | [[Category: Tbc]]
| + | |
| Structural highlights
Disease
TBC20_HUMAN Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
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.
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K. Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail. 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 doi:http://dx.doi.org/10.1073/pnas.1214431110
|
