3f9e: Difference between revisions
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==Crystal Structure of the S139A mutant of SARS-Coronovirus 3C-like Protease== | ==Crystal Structure of the S139A mutant of SARS-Coronovirus 3C-like Protease== | ||
<StructureSection load='3f9e' size='340' side='right' caption='[[3f9e]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='3f9e' size='340' side='right' caption='[[3f9e]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f9f|3f9f]], [[3f9g|3f9g]], [[3f9h|3f9h]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f9f|3f9f]], [[3f9g|3f9g]], [[3f9h|3f9h]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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=3f9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f9e OCA], [http://pdbe.org/3f9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f9e RCSB], [http://www.ebi.ac.uk/pdbsum/3f9e PDBsum]</span></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=3f9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f9e OCA], [http://pdbe.org/3f9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f9e RCSB], [http://www.ebi.ac.uk/pdbsum/3f9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f9e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/3f9e_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/3f9e_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> | ||
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[[Category: Li, L]] | [[Category: Li, L]] | ||
[[Category: Shen, X]] | [[Category: Shen, X]] | ||
[[Category: Cytoplasm]] | |||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
[[Category: Metal-binding]] | [[Category: Metal-binding]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
[[Category: Ribosomal frameshifting]] | |||
[[Category: Rna-binding]] | [[Category: Rna-binding]] | ||
[[Category: Thiol protease]] | [[Category: Thiol protease]] | ||
[[Category: Transmembrane]] | [[Category: Transmembrane]] | ||
[[Category: Zinc]] | |||
[[Category: Zinc-finger]] | [[Category: Zinc-finger]] | ||
Revision as of 10:20, 5 December 2018
Crystal Structure of the S139A mutant of SARS-Coronovirus 3C-like ProteaseCrystal Structure of the S139A mutant of SARS-Coronovirus 3C-like Protease
Structural highlights
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 PubMedThe 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CL(pro). S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro). Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure.,Hu T, Zhang Y, Li L, Wang K, Chen S, Chen J, Ding J, Jiang H, Shen X Virology. 2009 Jun 5;388(2):324-34. Epub 2009 May 5. PMID:19409595[13] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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