View source for 9pad


==Crystal structure of IBV-3CLpro with ALG-097608 (Inhibitor 1)==
<StructureSection load='9pad' size='340' side='right'caption='[[9pad]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9pad]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Infectious_bronchitis_virus Infectious bronchitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PAD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CHF:(1~{R},2~{R},3~{S},6~{S},7~{S})-~{N}-[(2~{R})-1-azanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]-4-[(2~{S})-3,3-dimethyl-2-[2,2,2-tris(fluoranyl)ethanoylamino]butanoyl]-10,10-bis(fluoranyl)-4-azatricyclo[5.2.1.0^{2,6}]dec-8-ene-3-carboxamide'>A1CHF</scene></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=9pad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pad OCA], [https://pdbe.org/9pad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pad RCSB], [https://www.ebi.ac.uk/pdbsum/9pad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pad ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A1P8SSX4_9GAMC A0A1P8SSX4_9GAMC] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[ARBA:ARBA00002182]  Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[ARBA:ARBA00003443]  Forms a primer, NSP9-pU, which is utilized by the polymerase for the initiation of RNA chains. Interacts with ribosome signal recognition particle RNA (SRP). Together with NSP8, suppress protein integration into the cell membrane, thereby disrupting host immune defenses.[ARBA:ARBA00043928]  May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[ARBA:ARBA00003115]  Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[ARBA:ARBA00024700]  Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[ARBA:ARBA00002697]  Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone is able to induce paired membranes. Coexpression of nsp3 and nsp4 does not result in the formation of DMVs.[ARBA:ARBA00045257]  RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA. The kinase-like NiRAN domain of NSP12 attaches one or more nucleotides to the amino terminus of NSP9, forming a covalent RNA-protein intermediate that serves as transcription/replication primer. Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion. This creates a series of subgenomic RNAs that are replicated, transcribed and translated. In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA.[ARBA:ARBA00043918]  Responsible for the cleavages located at the N-terminus of the 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.[ARBA:ARBA00045592]
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</StructureSection>
[[Category: Infectious bronchitis virus]]
[[Category: Large Structures]]
[[Category: Forouhad F]]
[[Category: Reddem ER]]
[[Category: Shapiro L]]
[[Category: Stoycheva A]]