4n14

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:30, 1 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==Crystal structure of Cdc20 and apcin complex==
==Crystal structure of Cdc20 and apcin complex==
-
<StructureSection load='4n14' size='340' side='right' caption='[[4n14]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+
<StructureSection load='4n14' size='340' side='right'caption='[[4n14]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4n14]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N14 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N14 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4n14]] 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=4N14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N14 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WR7:2-(2-METHYL-5-NITRO-1H-IMIDAZOL-1-YL)ETHYL+[(1R)-2,2,2-TRICHLORO-1-(PYRIMIDIN-2-YLAMINO)ETHYL]CARBAMATE'>WR7</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]] 2.1&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gga|4gga]], [[4ggc|4ggc]], [[4ggd|4ggd]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=WR7:2-(2-METHYL-5-NITRO-1H-IMIDAZOL-1-YL)ETHYL+[(1R)-2,2,2-TRICHLORO-1-(PYRIMIDIN-2-YLAMINO)ETHYL]CARBAMATE'>WR7</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=4n14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n14 OCA], [http://pdbe.org/4n14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n14 RCSB], [http://www.ebi.ac.uk/pdbsum/4n14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n14 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=4n14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n14 OCA], [https://pdbe.org/4n14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n14 RCSB], [https://www.ebi.ac.uk/pdbsum/4n14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n14 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/CDC20_HUMAN CDC20_HUMAN]] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.<ref>PMID:9811605</ref> <ref>PMID:9734353</ref> <ref>PMID:9637688</ref>
+
[https://www.uniprot.org/uniprot/CDC20_HUMAN CDC20_HUMAN] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.<ref>PMID:9811605</ref> <ref>PMID:9734353</ref> <ref>PMID:9637688</ref>
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-l-arginine methyl ester, a small molecule that blocks the APC/C-Cdc20 interaction. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine.
+
-
 
+
-
Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C.,Sackton KL, Dimova N, Zeng X, Tian W, Zhang M, Sackton TB, Meaders J, Pfaff KL, Sigoillot F, Yu H, Luo X, King RW Nature. 2014 Aug 24. doi: 10.1038/nature13660. PMID:25156254<ref>PMID:25156254</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4n14" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Luo, X]]
+
[[Category: Homo sapiens]]
-
[[Category: Tian, W]]
+
[[Category: Large Structures]]
-
[[Category: Yu, H]]
+
[[Category: Luo X]]
-
[[Category: Cell cycle]]
+
[[Category: Tian W]]
-
[[Category: Cell cycle-cell cycle inhibitor complex]]
+
[[Category: Yu H]]
-
[[Category: Mitosis]]
+
-
[[Category: Securin]]
+
-
[[Category: Ubiquitination]]
+
-
[[Category: Wd40]]
+

Current revision

Crystal structure of Cdc20 and apcin complex

PDB ID 4n14

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4n14"
Personal tools