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==Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide in space group P212121==
==Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide in space group P212121==
<StructureSection load='2a5k' size='340' side='right' caption='[[2a5k]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='2a5k' size='340' side='right'caption='[[2a5k]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a5k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A5K FirstGlance]. <br>
<table><tr><td colspan='2'>[[2a5k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A5K FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZP:(5S,8S,14R)-ETHYL+11-(3-AMINO-3-OXOPROPYL)-8-BENZYL-14-HYDROXY-5-ISOBUTYL-3,6,9,12-TETRAOXO-1-PHENYL-2-OXA-4,7,10,11-TETRAAZAPENTADECAN-15-OATE'>AZP</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]] 2.3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2a5a|2a5a]], [[2a5i|2a5i]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZP:(5S,8S,14R)-ETHYL+11-(3-AMINO-3-OXOPROPYL)-8-BENZYL-14-HYDROXY-5-ISOBUTYL-3,6,9,12-TETRAOXO-1-PHENYL-2-OXA-4,7,10,11-TETRAAZAPENTADECAN-15-OATE'>AZP</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=2a5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5k OCA], [http://pdbe.org/2a5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a5k RCSB], [http://www.ebi.ac.uk/pdbsum/2a5k PDBsum]</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=2a5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5k OCA], [https://pdbe.org/2a5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a5k RCSB], [https://www.ebi.ac.uk/pdbsum/2a5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5k ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/R1AB_CVHSA R1AB_CVHSA]] 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 (By similarity).<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  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.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  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). Activity of helicase is dependent on magnesium.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>   Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> 
[https://www.uniprot.org/uniprot/R1AB_SARS R1AB_SARS] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.  Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).<ref>PMID:23035226</ref> <ref>PMID:30943371</ref>   May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.<ref>PMID:19640993</ref>  Responsible for the cleavages located at the N-terminus of the 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 (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.<ref>PMID:16271890</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref> <ref>PMID:24622840</ref> <ref>PMID:24410069</ref>  Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.<ref>PMID:23943763</ref> <ref>PMID:24410069</ref>  Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.[PROSITE-ProRule:PRU00772]<ref>PMID:16226257</ref>   Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).<ref>PMID:24991833</ref> <ref>PMID:24410069</ref>  Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref>   Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.<ref>PMID:22039154</ref>   May participate in viral replication by acting as a ssRNA-binding protein.<ref>PMID:19153232</ref>  Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.<ref>PMID:22635272</ref>  Responsible for replication and transcription of the viral RNA genome.<ref>PMID:22791111</ref>   Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.<ref>PMID:12917423</ref> <ref>PMID:22615777</ref>  Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585).<ref>PMID:16549795</ref> <ref>PMID:20421945</ref> <ref>PMID:21593585</ref> <ref>PMID:22635272</ref> <ref>PMID:23966862</ref> <ref>PMID:29511076</ref>  Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.  Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.<ref>PMID:18417574</ref> <ref>PMID:20421945</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a5/2a5k_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a5/2a5k_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
Line 30: Line 31:


==See Also==
==See Also==
*[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cvhsa]]
[[Category: Large Structures]]
[[Category: Cherney, M M]]
[[Category: Severe acute respiratory syndrome-related coronavirus]]
[[Category: Eltis, L D]]
[[Category: Cherney MM]]
[[Category: Huitema, C]]
[[Category: Eltis LD]]
[[Category: James, K E]]
[[Category: Huitema C]]
[[Category: James, M N]]
[[Category: James KE]]
[[Category: Lee, T W]]
[[Category: James MN]]
[[Category: Liu, J]]
[[Category: Lee T-W]]
[[Category: Powers, J C]]
[[Category: Liu J]]
[[Category: 3c-like]]
[[Category: Powers JC]]
[[Category: Alpha-helical domain]]
[[Category: Aza-peptide epoxide]]
[[Category: C-s covalent bond]]
[[Category: Catalytic dyad]]
[[Category: Chymotrypsin-like fold]]
[[Category: Cysteine peptidase]]
[[Category: Dimer]]
[[Category: Epoxide stereochemistry]]
[[Category: Hydrolase]]
[[Category: Long loop]]
[[Category: N-finger]]
[[Category: Specificity pocket]]
[[Category: Substrate-like inhibitor]]

Latest revision as of 10:19, 23 August 2023

Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide in space group P212121Crystal structures of SARS coronavirus main peptidase inhibited by an aza-peptide epoxide in space group P212121

Structural highlights

2a5k is a 2 chain structure with sequence from Severe acute respiratory syndrome-related coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

R1AB_SARS Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).[1] [2] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[3] Responsible for the cleavages located at the N-terminus of the 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 (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.[4] [5] [6] [7] [8] Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.[9] [10] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.[PROSITE-ProRule:PRU00772][11] Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).[12] [13] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[14] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[15] May participate in viral replication by acting as a ssRNA-binding protein.[16] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[17] Responsible for replication and transcription of the viral RNA genome.[18] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[19] [20] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585).[21] [22] [23] [24] [25] [26] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[27] [28]

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

The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1).

Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide.,Lee TW, Cherney MM, Huitema C, Liu J, James KE, Powers JC, Eltis LD, James MN J Mol Biol. 2005 Nov 11;353(5):1137-51. Epub 2005 Sep 27. PMID:16219322[29]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Lokugamage KG, Narayanan K, Huang C, Makino S. Severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation. J Virol. 2012 Dec;86(24):13598-608. doi: 10.1128/JVI.01958-12. Epub 2012 Oct 3. PMID:23035226 doi:http://dx.doi.org/10.1128/JVI.01958-12
  2. ↑ Gomez GN, Abrar F, Dodhia MP, Gonzalez FG, Nag A. SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex. Biochem Cell Biol. 2019 Dec;97(6):758-766. doi: 10.1139/bcb-2018-0394. Epub 2019 , Apr 3. PMID:30943371 doi:http://dx.doi.org/10.1139/bcb-2018-0394
  3. ↑ Cornillez-Ty CT, Liao L, Yates JR 3rd, Kuhn P, Buchmeier MJ. Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. J Virol. 2009 Oct;83(19):10314-8. Epub 2009 Jul 29. PMID:19640993 doi:http://dx.doi.org/JVI.00842-09
  4. ↑ Saikatendu KS, Joseph JS, Subramanian V, Clayton T, Griffith M, Moy K, Velasquez J, Neuman BW, Buchmeier MJ, Stevens RC, Kuhn P. Structural basis of severe acute respiratory syndrome coronavirus ADP-ribose-1-phosphate dephosphorylation by a conserved domain of nsP3. Structure. 2005 Nov;13(11):1665-75. PMID:16271890 doi:10.1016/j.str.2005.07.022
  5. ↑ Lindner HA, Lytvyn V, Qi H, Lachance P, Ziomek E, Menard R. Selectivity in ISG15 and ubiquitin recognition by the SARS coronavirus papain-like protease. Arch Biochem Biophys. 2007 Oct 1;466(1):8-14. Epub 2007 Jul 14. PMID:17692280 doi:10.1016/j.abb.2007.07.006
  6. ↑ Frieman M, Ratia K, Johnston RE, Mesecar AD, Baric RS. Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J Virol. 2009 Jul;83(13):6689-705. doi: 10.1128/JVI.02220-08. Epub 2009 Apr 15. PMID:19369340 doi:10.1128/JVI.02220-08
  7. ↑ Chen X, Yang X, Zheng Y, Yang Y, Xing Y, Chen Z. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell. 2014 May;5(5):369-81. doi: 10.1007/s13238-014-0026-3. Epub 2014 Mar, 14. PMID:24622840 doi:http://dx.doi.org/10.1007/s13238-014-0026-3
  8. ↑ Angelini MM, Neuman BW, Buchmeier MJ. Untangling membrane rearrangement in the nidovirales. DNA Cell Biol. 2014 Mar;33(3):122-7. doi: 10.1089/dna.2013.2304. Epub 2014 Jan, 10. PMID:24410069 doi:http://dx.doi.org/10.1089/dna.2013.2304
  9. ↑ Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio. 2013 Aug 13;4(4). pii: mBio.00524-13. doi: 10.1128/mBio.00524-13. PMID:23943763 doi:http://dx.doi.org/10.1128/mBio.00524-13
  10. ↑ Angelini MM, Neuman BW, Buchmeier MJ. Untangling membrane rearrangement in the nidovirales. DNA Cell Biol. 2014 Mar;33(3):122-7. doi: 10.1089/dna.2013.2304. Epub 2014 Jan, 10. PMID:24410069 doi:http://dx.doi.org/10.1089/dna.2013.2304
  11. ↑ Lin CW, Tsai FJ, Wan L, Lai CC, Lin KH, Hsieh TH, Shiu SY, Li JY. Binding interaction of SARS coronavirus 3CL(pro) protease with vacuolar-H+ ATPase G1 subunit. FEBS Lett. 2005 Nov 7;579(27):6089-94. doi: 10.1016/j.febslet.2005.09.075. Epub, 2005 Oct 6. PMID:16226257 doi:http://dx.doi.org/10.1016/j.febslet.2005.09.075
  12. ↑ Cottam EM, Whelband MC, Wileman T. Coronavirus NSP6 restricts autophagosome expansion. Autophagy. 2014 Aug;10(8):1426-41. doi: 10.4161/auto.29309. Epub 2014 Jun 11. PMID:24991833 doi:http://dx.doi.org/10.4161/auto.29309
  13. ↑ Angelini MM, Neuman BW, Buchmeier MJ. Untangling membrane rearrangement in the nidovirales. DNA Cell Biol. 2014 Mar;33(3):122-7. doi: 10.1089/dna.2013.2304. Epub 2014 Jan, 10. PMID:24410069 doi:http://dx.doi.org/10.1089/dna.2013.2304
  14. ↑ te Velthuis AJ, van den Worm SH, Snijder EJ. The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res. 2012 Feb;40(4):1737-47. doi: 10.1093/nar/gkr893. Epub 2011 Oct, 29. PMID:22039154 doi:http://dx.doi.org/10.1093/nar/gkr893
  15. ↑ te Velthuis AJ, van den Worm SH, Snijder EJ. The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res. 2012 Feb;40(4):1737-47. doi: 10.1093/nar/gkr893. Epub 2011 Oct, 29. PMID:22039154 doi:http://dx.doi.org/10.1093/nar/gkr893
  16. ↑ Miknis ZJ, Donaldson EF, Umland TC, Rimmer RA, Baric RS, Schultz LW. Severe acute respiratory syndrome coronavirus nsp9 dimerization is essential for efficient viral growth. J Virol. 2009 Apr;83(7):3007-18. Epub 2009 Jan 19. PMID:19153232 doi:10.1128/JVI.01505-08
  17. ↑ Bouvet M, Imbert I, Subissi L, Gluais L, Canard B, Decroly E. RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9372-7. doi:, 10.1073/pnas.1201130109. Epub 2012 May 25. PMID:22635272 doi:http://dx.doi.org/10.1073/pnas.1201130109
  18. ↑ Ahn DG, Choi JK, Taylor DR, Oh JW. Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates. Arch Virol. 2012 Nov;157(11):2095-104. doi: 10.1007/s00705-012-1404-x. Epub 2012 , Jul 13. PMID:22791111 doi:http://dx.doi.org/10.1007/s00705-012-1404-x
  19. ↑ Tanner JA, Watt RM, Chai YB, Lu LY, Lin MC, Peiris JS, Poon LL, Kung HF, Huang JD. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5' to 3' viral helicases. J Biol Chem. 2003 Oct 10;278(41):39578-82. Epub 2003 Aug 13. PMID:12917423 doi:http://dx.doi.org/10.1074/jbc.C300328200
  20. ↑ Adedeji AO, Marchand B, Te Velthuis AJ, Snijder EJ, Weiss S, Eoff RL, Singh K, Sarafianos SG. Mechanism of nucleic acid unwinding by SARS-CoV helicase. PLoS One. 2012;7(5):e36521. doi: 10.1371/journal.pone.0036521. Epub 2012 May 15. PMID:22615777 doi:http://dx.doi.org/10.1371/journal.pone.0036521
  21. ↑ Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, Ziebuhr J. Discovery of an RNA virus 3'->5' exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5108-13. Epub 2006 Mar 20. PMID:16549795 doi:http://dx.doi.org/0508200103
  22. ↑ Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder EJ, Canard B, Decroly E. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog. 2010 Apr 22;6(4):e1000863. doi: 10.1371/journal.ppat.1000863. PMID:20421945 doi:http://dx.doi.org/10.1371/journal.ppat.1000863
  23. ↑ Denison MR, Graham RL, Donaldson EF, Eckerle LD, Baric RS. Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. RNA Biol. 2011 Mar-Apr;8(2):270-9. doi: 10.4161/rna.8.2.15013. Epub 2011 Mar 1. PMID:21593585 doi:http://dx.doi.org/10.4161/rna.8.2.15013
  24. ↑ Bouvet M, Imbert I, Subissi L, Gluais L, Canard B, Decroly E. RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9372-7. doi:, 10.1073/pnas.1201130109. Epub 2012 May 25. PMID:22635272 doi:http://dx.doi.org/10.1073/pnas.1201130109
  25. ↑ Smith EC, Blanc H, Surdel MC, Vignuzzi M, Denison MR. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLoS Pathog. 2013 Aug;9(8):e1003565. doi: 10.1371/journal.ppat.1003565. Epub 2013, Aug 15. PMID:23966862 doi:http://dx.doi.org/10.1371/journal.ppat.1003565
  26. ↑ Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: mBio.00221-18. doi: 10.1128/mBio.00221-18. PMID:29511076 doi:http://dx.doi.org/10.1128/mBio.00221-18
  27. ↑ Decroly E, Imbert I, Coutard B, Bouvet M, Selisko B, Alvarez K, Gorbalenya AE, Snijder EJ, Canard B. Coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'O)-methyltransferase activity. J Virol. 2008 Aug;82(16):8071-84. doi: 10.1128/JVI.00407-08. Epub 2008 Apr 16. PMID:18417574 doi:http://dx.doi.org/10.1128/JVI.00407-08
  28. ↑ Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder EJ, Canard B, Decroly E. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog. 2010 Apr 22;6(4):e1000863. doi: 10.1371/journal.ppat.1000863. PMID:20421945 doi:http://dx.doi.org/10.1371/journal.ppat.1000863
  29. ↑ Lee TW, Cherney MM, Huitema C, Liu J, James KE, Powers JC, Eltis LD, James MN. Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide. J Mol Biol. 2005 Nov 11;353(5):1137-51. Epub 2005 Sep 27. PMID:16219322 doi:10.1016/j.jmb.2005.09.004

2a5k, resolution 2.30Å

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