1p9u

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{{Seed}}
 
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[[Image:1p9u.png|left|200px]]
 
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==Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs==
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The line below this paragraph, containing "STRUCTURE_1p9u", creates the "Structure Box" on the page.
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<StructureSection load='1p9u' size='340' side='right'caption='[[1p9u]], [[Resolution|resolution]] 2.37&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'>[[1p9u]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Transmissible_gastroenteritis_virus Transmissible gastroenteritis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P9U FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_1p9u| PDB=1p9u | 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=1p9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9u OCA], [https://pdbe.org/1p9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p9u RCSB], [https://www.ebi.ac.uk/pdbsum/1p9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/R1AB_CVPPU R1AB_CVPPU] 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. The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 (By similarity). 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-|-[SAGC]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G). The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction (By similarity). Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity). Nsp9 is a ssRNA-binding protein (By similarity). NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p9/1p9u_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p9u ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS.
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===Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs===
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Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.,Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R Science. 2003 Jun 13;300(5626):1763-7. Epub 2003 May 13. PMID:12746549<ref>PMID:12746549</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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The line below this paragraph, {{ABSTRACT_PUBMED_12746549}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1p9u" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 12746549 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12746549}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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1P9U is a 8 chains structure of sequences from [http://en.wikipedia.org/wiki/Transmissible_gastroenteritis_virus Transmissible gastroenteritis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P9U OCA].
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==Reference==
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<ref group="xtra">PMID:12746549</ref><references group="xtra"/>
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[[Category: Transmissible gastroenteritis virus]]
[[Category: Transmissible gastroenteritis virus]]
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[[Category: Anand, K.]]
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[[Category: Anand K]]
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[[Category: Hilgenfeld, R.]]
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[[Category: Hilgenfeld R]]
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[[Category: Mesters, J R.]]
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[[Category: Mesters JR]]
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[[Category: Wadhwani, P.]]
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[[Category: Wadhwani P]]
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[[Category: Ziebuhr, J.]]
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[[Category: Ziebuhr J]]
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[[Category: Coronavirus]]
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[[Category: Hcov]]
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[[Category: Sars-cov]]
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[[Category: Tgev]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 17:53:26 2009''
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Current revision

Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of anti-SARS Drugs

PDB ID 1p9u

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