View source for 8zcc


==Crystal structure of HCoV-NL63 main protease with X77==
<StructureSection load='8zcc' size='340' side='right'caption='[[8zcc]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8zcc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_coronavirus_NL63 Human coronavirus NL63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZCC 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]] 1.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=X77:N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide'>X77</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=8zcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zcc OCA], [https://pdbe.org/8zcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zcc RCSB], [https://www.ebi.ac.uk/pdbsum/8zcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zcc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/R1AB_CVHNL R1AB_CVHNL] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.<ref>PMID:20181693</ref>   The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the 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).[PROSITE-ProRule:PRU00772]  The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G).<ref>PMID:20181693</ref>   The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.  Nsp9 is a ssRNA-binding protein.  NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human coronavirus NL63]]
[[Category: Large Structures]]
[[Category: Li J]]
[[Category: Li WW]]
[[Category: Xu J]]
[[Category: Yin XS]]