8d1t: Difference between revisions

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'''Unreleased structure'''


The entry 8d1t is ON HOLD
==Crystal structure of human USP30 in complex with a covalent inhibitor 552 and a Fab==
 
<StructureSection load='8d1t' size='340' side='right'caption='[[8d1t]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
Authors: Song, X., Butler, J., Li, C., Zhang, K., Zhang, D., Hao, Y.
== Structural highlights ==
 
<table><tr><td colspan='2'>[[8d1t]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8D1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D1T FirstGlance]. <br>
Description: Crystal structure of human USP30 in complex with a covalent inhibitor 552 and a Fab
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.94&#8491;</td></tr>
[[Category: Unreleased Structures]]
<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>, <scene name='pdbligand=PXW:(1R,2R,4S,7E)-7-[amino(sulfanyl)methylidene]-2-{[(1P)-3-chloro-3-(1-cyanocyclopropyl)[1,1-biphenyl]-4-carbonyl]amino}-7-azabicyclo[2.2.1]heptan-7-ium'>PXW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
[[Category: Butler, J]]
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8d1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d1t OCA], [https://pdbe.org/8d1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d1t RCSB], [https://www.ebi.ac.uk/pdbsum/8d1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d1t ProSAT]</span></td></tr>
[[Category: Li, C]]
</table>
[[Category: Zhang, D]]
== Function ==
[[Category: Hao, Y]]
[https://www.uniprot.org/uniprot/UBP30_HUMAN UBP30_HUMAN] Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy (PubMed:18287522, PubMed:24896179, PubMed:25527291, PubMed:25621951). Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate to mitophagic signaling (PubMed:25621951). Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65' (PubMed:25527291). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (By similarity).[UniProtKB:Q3UN04]<ref>PMID:18287522</ref> <ref>PMID:24896179</ref> <ref>PMID:25527291</ref> <ref>PMID:25621951</ref>
[[Category: Song, X]]
== References ==
[[Category: Zhang, K]]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Butler J]]
[[Category: Hao Y]]
[[Category: Li C]]
[[Category: Song X]]
[[Category: Zhang D]]
[[Category: Zhang K]]

Latest revision as of 13:05, 25 October 2023

Crystal structure of human USP30 in complex with a covalent inhibitor 552 and a FabCrystal structure of human USP30 in complex with a covalent inhibitor 552 and a Fab

Structural highlights

8d1t is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.94Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP30_HUMAN Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy (PubMed:18287522, PubMed:24896179, PubMed:25527291, PubMed:25621951). Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate to mitophagic signaling (PubMed:25621951). Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65' (PubMed:25527291). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (By similarity).[UniProtKB:Q3UN04][1] [2] [3] [4]

References

  1. ↑ Nakamura N, Hirose S. Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane. Mol Biol Cell. 2008 May;19(5):1903-11. Epub 2008 Feb 20. PMID:18287522 doi:http://dx.doi.org/E07-11-1103
  2. ↑ Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370-5. doi: 10.1038/nature13418. Epub 2014 Jun 4. PMID:24896179 doi:http://dx.doi.org/10.1038/nature13418
  3. ↑ Wauer T, Swatek KN, Wagstaff JL, Gladkova C, Pruneda JN, Michel MA, Gersch M, Johnson CM, Freund SM, Komander D. Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J. 2014 Dec 19. pii: e201489847. PMID:25527291 doi:http://dx.doi.org/10.15252/embj.201489847
  4. ↑ Cunningham CN, Baughman JM, Phu L, Tea JS, Yu C, Coons M, Kirkpatrick DS, Bingol B, Corn JE. USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Nat Cell Biol. 2015 Feb;17(2):160-9. doi: 10.1038/ncb3097. Epub 2015 Jan 26. PMID:25621951 doi:http://dx.doi.org/10.1038/ncb3097

8d1t, resolution 2.94Å

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