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3snb

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[[Image:3snb.jpg|left|200px]]
 
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==Crystal structure of SARS coronavirus main protease complexed with Ac-DSFDQ-H (soaking)==
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The line below this paragraph, containing "STRUCTURE_3snb", creates the "Structure Box" on the page.
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<StructureSection load='3snb' size='340' side='right'caption='[[3snb]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3snb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SNB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ECC:(4S)-4-AMINO-5-HYDROXYPENTANAMIDE'>ECC</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h2z|2h2z]], [[3sn8|3sn8]], [[3sna|3sna]], [[3snc|3snc]], [[3snd|3snd]], [[3sne|3sne]]</div></td></tr>
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{{STRUCTURE_3snb| PDB=3snb | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3snb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3snb OCA], [https://pdbe.org/3snb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3snb RCSB], [https://www.ebi.ac.uk/pdbsum/3snb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3snb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SARS coronavirus main protease (SARS-CoV M(pro)) is essential for the replication of the virus and regarded as a major antiviral drug target. The enzyme is a cysteine protease, with a catalytic dyad (Cys-145/His-41) in the active site. Aldehyde inhibitors can bind reversibly to the active-site sulfhydryl of SARS-CoV M(pro). Previous studies using peptidic substrates and inhibitors showed that the substrate specificity of SARS-CoV M(pro) requires glutamine in the P1 position and a large hydrophobic residue in the P2 position. We determined four crystal structures of SARS-CoV M(pro) in complex with pentapeptide aldehydes (Ac-ESTLQ-H, Ac-NSFSQ-H, Ac-DSFDQ-H, and Ac-NSTSQ-H). Kinetic data showed that all of these aldehydes exhibit inhibitory activity towards SARS-CoV M(pro), with K(i) values in the muM range. Surprisingly, the X-ray structures revealed that the hydrophobic S2 pocket of the enzyme can accommodate serine and even aspartic-acid side-chains in the P2 positions of the inhibitors. Consequently, we reassessed the substrate specificity of the enzyme by testing the cleavage of 20 different tetradecapeptide substrates with varying amino-acid residues in the P2 position. The cleavage efficiency for the substrate with serine in the P2 position was 160-times lower than that for the original substrate (P2=Leu); furthermore, the substrate with aspartic acid in the P2 position was not cleaved at all. We also determined a crystal structure of SARS-CoV M(pro) in complex with aldehyde Cm-FF-H, which has its P1-phenylalanine residue bound to the relatively hydrophilic S1 pocket of the enzyme and yet exhibits a high inhibitory activity against SARS-CoV M(pro), with K(i)=2.24+/-0.58muM. These results show that the stringent substrate specificity of the SARS-CoV M(pro) with respect to the P1 and P2 positions can be overruled by the highly electrophilic character of the aldehyde warhead, thereby constituting a deviation from the dogma that peptidic inhibitors need to correspond to the observed cleavage specificity of the target protease.
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===Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease===
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Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease.,Zhu L, George S, Schmidt MF, Al-Gharabli SI, Rademann J, Hilgenfeld R Antiviral Res. 2011 Aug 11. PMID:21854807<ref>PMID:21854807</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3snb" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_21854807}}, adds the Publication Abstract to the page
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*[[Virus protease 3D structures|Virus protease 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 21854807 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_21854807}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Cvhsa]]
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[[3snb]] 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=3SNB OCA].
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[[Category: Large Structures]]
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[[Category: Hilgenfeld, R]]
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==Reference==
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[[Category: Zhu, L]]
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<ref group="xtra">PMID:021854807</ref><references group="xtra"/>
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[[Category: Sars coronavirus]]
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[[Category: Hilgenfeld, R.]]
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[[Category: Zhu, L.]]
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[[Category: 3c-like proteinase]]
[[Category: 3c-like proteinase]]
[[Category: Ac-dsfdq-h]]
[[Category: Ac-dsfdq-h]]

Current revision

Crystal structure of SARS coronavirus main protease complexed with Ac-DSFDQ-H (soaking)

PDB ID 3snb

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