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2gti

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[[Image:2gti.gif|left|200px]]
 
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==mutation of MHV coronavirus non-structural protein nsp15 (F307L)==
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The line below this paragraph, containing "STRUCTURE_2gti", creates the "Structure Box" on the page.
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<StructureSection load='2gti' size='340' side='right'caption='[[2gti]], [[Resolution|resolution]] 2.15&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'>[[2gti]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvma5 Cvma5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GTI FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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{{STRUCTURE_2gti| PDB=2gti | 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=2gti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gti OCA], [https://pdbe.org/2gti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gti RCSB], [https://www.ebi.ac.uk/pdbsum/2gti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gti ProSAT]</span></td></tr>
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</table>
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'''mutation of MHV coronavirus non-structural protein nsp15 (F307L)'''
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== Function ==
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[[https://www.uniprot.org/uniprot/R1AB_CVMA5 R1AB_CVMA5]] 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 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent 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-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). 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) (By similarity). 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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==Overview==
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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/gt/2gti_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2gti 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 ==
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded nonstructural proteins (nsp) plays a vital role during initial and intermediate phases of the viral life cycle. The crystal structure of mouse hepatitis virus strain A59 (MHV-A59) nsp15 is reported at 2.15-A resolution. nsp15 is an XendoU endoribonuclease and is the first one from this family to have its structure unveiled. The MHV-A59 nsp15 monomer structure has a novel protein fold. Two nsp15 trimers form a back-to-back hexamer that is believed to be the functional unit. The structure reveals the catalytic site including the highly conserved residues His262, His277, and Lys317, which is supported by mutagenesis analysis. Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate. The high sequence conservation of nsp15 in coronaviruses, including that of severe acute respiratory syndrome, suggests that this protein may provide a new target for the design of antiviral therapeutics.
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded nonstructural proteins (nsp) plays a vital role during initial and intermediate phases of the viral life cycle. The crystal structure of mouse hepatitis virus strain A59 (MHV-A59) nsp15 is reported at 2.15-A resolution. nsp15 is an XendoU endoribonuclease and is the first one from this family to have its structure unveiled. The MHV-A59 nsp15 monomer structure has a novel protein fold. Two nsp15 trimers form a back-to-back hexamer that is believed to be the functional unit. The structure reveals the catalytic site including the highly conserved residues His262, His277, and Lys317, which is supported by mutagenesis analysis. Gel filtration and enzyme activity assays confirmed that the hexamer is the active form for nsp15 and demonstrate the specificity of nsp15 for uridylate. The high sequence conservation of nsp15 in coronaviruses, including that of severe acute respiratory syndrome, suggests that this protein may provide a new target for the design of antiviral therapeutics.
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==About this Structure==
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New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15.,Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A, Zhang XC, Bartlam M, Rao Z J Virol. 2006 Aug;80(16):7909-17. PMID:16873248<ref>PMID:16873248</ref>
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2GTI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Murine_hepatitis_virus Murine hepatitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTI OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15., Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A, Zhang XC, Bartlam M, Rao Z, J Virol. 2006 Aug;80(16):7909-17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16873248 16873248]
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</div>
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[[Category: Murine hepatitis virus]]
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<div class="pdbe-citations 2gti" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Lou, Z.]]
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<references/>
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[[Category: Rao, Z.]]
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__TOC__
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[[Category: Su, D.]]
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</StructureSection>
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[[Category: Sun, F.]]
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[[Category: Cvma5]]
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[[Category: Xu, X.]]
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[[Category: Large Structures]]
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[[Category: Zhai, Y.]]
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[[Category: Lou, Z]]
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[[Category: Rao, Z]]
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[[Category: Su, D]]
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[[Category: Sun, F]]
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[[Category: Xu, X]]
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[[Category: Zhai, Y]]
[[Category: F307l]]
[[Category: F307l]]
[[Category: Mhv]]
[[Category: Mhv]]
[[Category: Nsp15]]
[[Category: Nsp15]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:30:59 2008''
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[[Category: Viral protein]]

Current revision

mutation of MHV coronavirus non-structural protein nsp15 (F307L)

PDB ID 2gti

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