2bx4

From Proteopedia

(Difference between revisions)

Revision as of 09:44, 5 May 2021

Crystal Structure of SARS Coronavirus Main Proteinase (P21212)

Structural highlights

2bx4 is a 1 chain structure with sequence from Sars coronavirus sin2774. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1o5s, 1p4x, 1p76, 1p9s, 1p9t, 1p9u, 1pa5, 1puk, 1q1x, 1q2w, 1q4z, 1qz8, 1ssk, 1sxf, 1uj1, 1uk2, 1uk3, 1uk4, 1uw7, 1wnc, 1xak, 1xjp, 1xjr, 2bw6, 2bx3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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 SARS coronavirus main proteinase (M(pro)) is a key enzyme in the processing of the viral polyproteins and thus an attractive target for the discovery of drugs directed against SARS. The enzyme has been shown by X-ray crystallography to undergo significant pH-dependent conformational changes. Here, we assess the conformational flexibility of the M(pro) by analysis of multiple crystal structures (including two new crystal forms) and by molecular dynamics (MD) calculations. The MD simulations take into account the different protonation states of two histidine residues in the substrate-binding site and explain the pH-activity profile of the enzyme. The low enzymatic activity of the M(pro) monomer and the need for dimerization are also discussed.

pH-dependent conformational flexibility of the SARS-CoV main proteinase (M(pro)) dimer: molecular dynamics simulations and multiple X-ray structure analyses.,Tan J, Verschueren KH, Anand K, Shen J, Yang M, Xu Y, Rao Z, Bigalke J, Heisen B, Mesters JR, Chen K, Shen X, Jiang H, Hilgenfeld R J Mol Biol. 2005 Nov 18;354(1):25-40. Epub 2005 Sep 23. PMID:16242152^[13]

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

References

↑ 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
↑ Tan J, Verschueren KH, Anand K, Shen J, Yang M, Xu Y, Rao Z, Bigalke J, Heisen B, Mesters JR, Chen K, Shen X, Jiang H, Hilgenfeld R. pH-dependent conformational flexibility of the SARS-CoV main proteinase (M(pro)) dimer: molecular dynamics simulations and multiple X-ray structure analyses. J Mol Biol. 2005 Nov 18;354(1):25-40. Epub 2005 Sep 23. PMID:16242152 doi:10.1016/j.jmb.2005.09.012

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bx4"

@@ Line 3: / Line 3: @@
 <StructureSection load='2bx4' size='340' side='right'caption='[[2bx4]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2bx4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus_sin2774 Sars coronavirus sin2774]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BX4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2bx4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sars_coronavirus_sin2774 Sars coronavirus sin2774]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BX4 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1o5s|1o5s]], [[1p4x|1p4x]], [[1p76|1p76]], [[1p9s|1p9s]], [[1p9t|1p9t]], [[1p9u|1p9u]], [[1pa5|1pa5]], [[1puk|1puk]], [[1q1x|1q1x]], [[1q2w|1q2w]], [[1q4z|1q4z]], [[1qz8|1qz8]], [[1ssk|1ssk]], [[1sxf|1sxf]], [[1uj1|1uj1]], [[1uk2|1uk2]], [[1uk3|1uk3]], [[1uk4|1uk4]], [[1uw7|1uw7]], [[1wnc|1wnc]], [[1xak|1xak]], [[1xjp|1xjp]], [[1xjr|1xjr]], [[2bw6|2bw6]], [[2bx3|2bx3]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1o5s|1o5s]], [[1p4x|1p4x]], [[1p76|1p76]], [[1p9s|1p9s]], [[1p9t|1p9t]], [[1p9u|1p9u]], [[1pa5|1pa5]], [[1puk|1puk]], [[1q1x|1q1x]], [[1q2w|1q2w]], [[1q4z|1q4z]], [[1qz8|1qz8]], [[1ssk|1ssk]], [[1sxf|1sxf]], [[1uj1|1uj1]], [[1uk2|1uk2]], [[1uk3|1uk3]], [[1uk4|1uk4]], [[1uw7|1uw7]], [[1wnc|1wnc]], [[1xak|1xak]], [[1xjp|1xjp]], [[1xjr|1xjr]], [[2bw6|2bw6]], [[2bx3|2bx3]]</div></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=2bx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bx4 OCA], [http://pdbe.org/2bx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bx4 RCSB], [http://www.ebi.ac.uk/pdbsum/2bx4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bx4 ProSAT]</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=2bx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bx4 OCA], [https://pdbe.org/2bx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bx4 RCSB], [https://www.ebi.ac.uk/pdbsum/2bx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bx4 ProSAT]</span></td></tr>
 </table>
 == 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>
+[[https://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 30: @@
 ==See Also==
-*[[SARS Coronavirus Main Proteinase|SARS Coronavirus Main Proteinase]]
+*[[Virus protease 3D structures|Virus protease 3D structures]]
 == References ==
 <references/>

2bx4

From Proteopedia

Revision as of 09:44, 5 May 2021

Crystal Structure of SARS Coronavirus Main Proteinase (P21212)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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