View source for 7hil


==Group deposition of Chikungunya virus nsP3 macrodomain in complex with inhibitors from the READDI-AC AViDD center -- Crystal structure of Chikungunya virus nsP3 macrodomain in complex with RA-0188488-01 (CHIKV_MacB-x2129)==
<StructureSection load='7hil' size='340' side='right'caption='[[7hil]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7hil]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus Chikungunya virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7HIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7HIL 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BCF:1-ethyl-~{N}-methyl-6-oxidanylidene-~{N}-(1,3-thiazol-2-ylmethyl)pyridazine-3-carboxamide'>A1BCF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7hil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7hil OCA], [https://pdbe.org/7hil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7hil RCSB], [https://www.ebi.ac.uk/pdbsum/7hil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7hil ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLN_CHIKS POLN_CHIKS] P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex (By similarity).  nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity).  nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins (By similarity). Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.  nsP3 is essential for minus strand and subgenomic 26S mRNA synthesis (By similarity).  nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins (By similarity).
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</StructureSection>
[[Category: Chikungunya virus]]
[[Category: Large Structures]]
[[Category: Almahli H]]
[[Category: Aschenbrenner JC]]
[[Category: Balcomb BH]]
[[Category: Capkin E]]
[[Category: Chandran AV]]
[[Category: Chen W]]
[[Category: Fairhead M]]
[[Category: Fearon D]]
[[Category: Godoy AS]]
[[Category: Golding M]]
[[Category: Koekemoer L]]
[[Category: Lithgo RM]]
[[Category: Marples PG]]
[[Category: Ni X]]
[[Category: Saleem RSZ]]
[[Category: Thompson W]]
[[Category: Todd MH]]
[[Category: Tomlinson CWE]]
[[Category: Wild C]]
[[Category: Winokan M]]
[[Category: Xavier M-AE]]
[[Category: Von Delft F]]