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{{STRUCTURE_2ynb|  PDB=2ynb  |  SCENE=  }}
===Crystal structure of the main protease of coronavirus HKU4 in complex with a Michael acceptor SG85===


==Function==
==Crystal structure of the main protease of coronavirus HKU4 in complex with a Michael acceptor SG85==
[[http://www.uniprot.org/uniprot/R1A_BCHK4 R1A_BCHK4]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity).  The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity).  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).  Nsp9 is a ssRNA-binding protein (By similarity).  Non-structural protein 1: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity).  
<StructureSection load='2ynb' size='340' side='right'caption='[[2ynb]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ynb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tylonycteris_bat_coronavirus_HKU4 Tylonycteris bat coronavirus HKU4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YNB 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]] 1.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G85:N-[(BENZYLOXY)CARBONYL]-O-TERT-BUTYL-L-SERYL-N-{(2R)-5-ETHOXY-5-OXO-1-[(3S)-2-OXOPYRROLIDIN-3-YL]PENTAN-2-YL}-L-PHENYLALANINAMIDE'>G85</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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=2ynb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ynb OCA], [https://pdbe.org/2ynb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ynb RCSB], [https://www.ebi.ac.uk/pdbsum/2ynb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ynb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/R1A_BCHK4 R1A_BCHK4] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3 (By similarity).  The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity).  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).  Nsp9 is a ssRNA-binding protein (By similarity).  Non-structural protein 1: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity).


==About this Structure==
==See Also==
[[2ynb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tylonycteris_bat_coronavirus_hku4 Tylonycteris bat coronavirus hku4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YNB OCA].
*[[Virus protease 3D structures|Virus protease 3D structures]]
[[Category: SARS coronavirus main proteinase]]
__TOC__
[[Category: Tylonycteris bat coronavirus hku4]]
</StructureSection>
[[Category: Hilgenfeld, R.]]
[[Category: Large Structures]]
[[Category: Ma, Q.]]
[[Category: Tylonycteris bat coronavirus HKU4]]
[[Category: Xiao, Y.]]
[[Category: Hilgenfeld R]]
[[Category: Hydrolase]]
[[Category: Ma Q]]
[[Category: Michael acceptor]]
[[Category: Xiao Y]]
[[Category: Sar]]

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