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| - | [[Image:1i7k.gif|left|200px]]<br /> | |
| - | <applet load="1i7k" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1i7k, resolution 1.95Å" /> | |
| - | '''CRYSTAL STRUCTURE OF HUMAN MITOTIC-SPECIFIC UBIQUITIN-CONJUGATING ENZYME, UBCH10'''<br /> | |
| | | | |
| - | ==Overview== | + | ==CRYSTAL STRUCTURE OF HUMAN MITOTIC-SPECIFIC UBIQUITIN-CONJUGATING ENZYME, UBCH10== |
| - | Cell cycle progression is controlled at several different junctures by the, targeted destruction of cell cycle regulatory proteins. These carefully, orchestrated events include the destruction of the securin protein to, permit entry into anaphase, and the destruction of cyclin B to permit exit, from mitosis. These destruction events are mediated by the, ubiquitin/proteasome system. The human ubiquitin-conjugating enzyme, UbcH10, is an essential mediator of the mitotic destruction events. We, report here the 1.95-A crystal structure of a mutant UbcH10, in which the, active site cysteine has been replaced with a serine. Functional analysis, indicates that the mutant is active in accepting ubiquitin, although not, as efficiently as wild-type. Examination of the crystal structure reveals, that the NH2-terminal extension in UbcH10 is disordered and that a, conserved 3(10)-helix places a lysine residue near the active site., Analysis of relevant mutants demonstrates that for ubiquitin-adduct, formation the presence or absence of the NH2-terminal extension has little, effect, whereas the lysine residue near the active site has significant, effect. The structure provides additional insight into UbcH10 function, including possible sites of interaction with the anaphase promoting, complex/cyclosome and the disposition of a putative destruction box motif, in the structure. | + | <StructureSection load='1i7k' size='340' side='right'caption='[[1i7k]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1i7k]] 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=1I7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I7K FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</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=1i7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7k OCA], [https://pdbe.org/1i7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i7k RCSB], [https://www.ebi.ac.uk/pdbsum/1i7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i7k ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/UBE2C_HUMAN UBE2C_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit.<ref>PMID:15558010</ref> <ref>PMID:18485873</ref> <ref>PMID:19820702</ref> <ref>PMID:19822757</ref> <ref>PMID:20061386</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i7/1i7k_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i7k ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Cell cycle progression is controlled at several different junctures by the targeted destruction of cell cycle regulatory proteins. These carefully orchestrated events include the destruction of the securin protein to permit entry into anaphase, and the destruction of cyclin B to permit exit from mitosis. These destruction events are mediated by the ubiquitin/proteasome system. The human ubiquitin-conjugating enzyme, UbcH10, is an essential mediator of the mitotic destruction events. We report here the 1.95-A crystal structure of a mutant UbcH10, in which the active site cysteine has been replaced with a serine. Functional analysis indicates that the mutant is active in accepting ubiquitin, although not as efficiently as wild-type. Examination of the crystal structure reveals that the NH2-terminal extension in UbcH10 is disordered and that a conserved 3(10)-helix places a lysine residue near the active site. Analysis of relevant mutants demonstrates that for ubiquitin-adduct formation the presence or absence of the NH2-terminal extension has little effect, whereas the lysine residue near the active site has significant effect. The structure provides additional insight into UbcH10 function including possible sites of interaction with the anaphase promoting complex/cyclosome and the disposition of a putative destruction box motif in the structure. |
| | | | |
| - | ==About this Structure==
| + | Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.,Lin Y, Hwang WC, Basavappa R J Biol Chem. 2002 Jun 14;277(24):21913-21. Epub 2002 Apr 1. PMID:11927573<ref>PMID:11927573</ref> |
| - | 1I7K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I7K OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10., Lin Y, Hwang WC, Basavappa R, J Biol Chem. 2002 Jun 14;277(24):21913-21. Epub 2002 Apr 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11927573 11927573]
| + | </div> |
| - | [[Category: Homo sapiens]]
| + | <div class="pdbe-citations 1i7k" style="background-color:#fffaf0;"></div> |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Ubiquitin--protein ligase]]
| + | |
| - | [[Category: Basavappa, R.]]
| + | |
| - | [[Category: Lin, Y.]]
| + | |
| - | [[Category: ubiquitin conjugating enzyme]]
| + | |
| | | | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:27:08 2007''
| + | ==See Also== |
| | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Basavappa R]] |
| | + | [[Category: Lin Y]] |
| Structural highlights
Function
UBE2C_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit.[1] [2] [3] [4] [5]
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
Cell cycle progression is controlled at several different junctures by the targeted destruction of cell cycle regulatory proteins. These carefully orchestrated events include the destruction of the securin protein to permit entry into anaphase, and the destruction of cyclin B to permit exit from mitosis. These destruction events are mediated by the ubiquitin/proteasome system. The human ubiquitin-conjugating enzyme, UbcH10, is an essential mediator of the mitotic destruction events. We report here the 1.95-A crystal structure of a mutant UbcH10, in which the active site cysteine has been replaced with a serine. Functional analysis indicates that the mutant is active in accepting ubiquitin, although not as efficiently as wild-type. Examination of the crystal structure reveals that the NH2-terminal extension in UbcH10 is disordered and that a conserved 3(10)-helix places a lysine residue near the active site. Analysis of relevant mutants demonstrates that for ubiquitin-adduct formation the presence or absence of the NH2-terminal extension has little effect, whereas the lysine residue near the active site has significant effect. The structure provides additional insight into UbcH10 function including possible sites of interaction with the anaphase promoting complex/cyclosome and the disposition of a putative destruction box motif in the structure.
Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.,Lin Y, Hwang WC, Basavappa R J Biol Chem. 2002 Jun 14;277(24):21913-21. Epub 2002 Apr 1. PMID:11927573[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rape M, Kirschner MW. Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature. 2004 Dec 2;432(7017):588-95. Epub 2004 Nov 21. PMID:15558010 doi:http://dx.doi.org/10.1038/nature03023
- ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
- ↑ Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J, Russell P, Pines J, Venkitaraman AR. UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nat Cell Biol. 2009 Nov;11(11):1363-9. doi: 10.1038/ncb1983. Epub 2009 Oct 11. PMID:19820702 doi:http://dx.doi.org/10.1038/ncb1983
- ↑ Williamson A, Wickliffe KE, Mellone BG, Song L, Karpen GH, Rape M. Identification of a physiological E2 module for the human anaphase-promoting complex. Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18213-8. doi:, 10.1073/pnas.0907887106. Epub 2009 Oct 12. PMID:19822757 doi:http://dx.doi.org/10.1073/pnas.0907887106
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ Lin Y, Hwang WC, Basavappa R. Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10. J Biol Chem. 2002 Jun 14;277(24):21913-21. Epub 2002 Apr 1. PMID:11927573 doi:10.1074/jbc.M109398200
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