3mj5
From Proteopedia
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===Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation=== | ===Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation=== | ||
+ | {{ABSTRACT_PUBMED_20527968}} | ||
- | + | ==Function== | |
- | + | [[http://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] 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> 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> | |
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==About this Structure== | ==About this Structure== | ||
- | + | [[3mj5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MJ5 OCA]. | |
==Reference== | ==Reference== | ||
- | <ref group="xtra">PMID: | + | <ref group="xtra">PMID:020527968</ref><references group="xtra"/><references/> |
[[Category: Sars coronavirus]] | [[Category: Sars coronavirus]] | ||
[[Category: Mesecar, A D.]] | [[Category: Mesecar, A D.]] | ||
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[[Category: Viral protein]] | [[Category: Viral protein]] | ||
[[Category: Zinc-finger]] | [[Category: Zinc-finger]] | ||
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- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 14 15:55:45 2010'' |
Revision as of 21:03, 17 April 2013
Contents |
Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation
Template:ABSTRACT PUBMED 20527968
Function
[R1A_CVHSA] 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.[1] [2] [3] 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.[4] [5] [6] Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.[7] [8] [9] Nsp9 is a ssRNA-binding protein.[10] [11] [12]
About this Structure
3mj5 is a 2 chain structure with sequence from Sars coronavirus. Full crystallographic information is available from OCA.
Reference
- Ghosh AK, Takayama J, Rao KV, Ratia K, Chaudhuri R, Mulhearn DC, Lee H, Nichols DB, Baliji S, Baker SC, Johnson ME, Mesecar AD. Severe Acute Respiratory Syndrome Coronavirus Papain-like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation. J Med Chem. 2010 Jun 9. PMID:20527968 doi:10.1021/jm1004489
- ↑ Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J. 2006 Oct 18;25(20):4933-42. Epub 2006 Oct 5. PMID:17024178 doi:7601368
- ↑ 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
- ↑ 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
- ↑ Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J. 2006 Oct 18;25(20):4933-42. Epub 2006 Oct 5. PMID:17024178 doi:7601368
- ↑ 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
- ↑ 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
- ↑ Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J. 2006 Oct 18;25(20):4933-42. Epub 2006 Oct 5. PMID:17024178 doi:7601368
- ↑ 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
- ↑ 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
- ↑ Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J. 2006 Oct 18;25(20):4933-42. Epub 2006 Oct 5. PMID:17024178 doi:7601368
- ↑ 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
- ↑ 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