8ze4
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==MPXV mRNA cap N7 methyltransferase mutant-H122D== | |
| + | <StructureSection load='8ze4' size='340' side='right'caption='[[8ze4]], [[Resolution|resolution]] 3.33Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8ze4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Monkeypox_virus Monkeypox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZE4 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]] 3.33Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=8ze4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ze4 OCA], [https://pdbe.org/8ze4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ze4 RCSB], [https://www.ebi.ac.uk/pdbsum/8ze4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ze4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MCEL_MONPV MCEL_MONPV] Catalytic subunit of the mRNA capping enzyme which catalyzes three enzymatic reactions: the 5' triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA 5' triphosphatase; the diphosphate RNA end is capped with GMP by RNA guanylyltransferase and the GpppN cap is methylated by RNA (guanine-N7) methyltransferase. Heterodimeric mRNA capping enzyme catalyzes the linkage of a N7-methyl-guanosine moiety to the first transcribed nucleotide (cap 0 structure), whereas the methyltransferase OPG102 is responsible for a second methylation at the 2'-O position of the ribose (cap 1 structure). Also involved in early viral gene transcription termination and intermediate viral gene transcription initiation. Early gene transcription termination requires the termination factor VTF, the DNA-dependent ATPase NPH-I/OPG123 and the RAP94/OPG109 subunit of the viral RNA polymerase, as well as the presence of a specific termination motif. Binds, together with RAP94/OPG109, to the termination motif 5'-UUUUUNU-3' in the nascent early mRNA.[UniProtKB:P04298] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The global outbreak of Mpox, caused by the monkeypox virus (MPXV), has attracted international attention and become another major infectious disease event after COVID-19. The mRNA cap N7 methyltransferase (RNMT) of MPXV methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs and plays a vital role in evading host antiviral immunity. MPXV RNMT is composed of the large subunit E1 and the small subunit E12. How E1 and E12 of MPXV assembly remains unclear. Here, we report the crystal structures of E12, the MTase domain of E1 with E12 (E1(CTD)-E12) complex, and the E1(CTD)-E12-SAM ternary complex, revealing the detailed conformations of critical residues and the structural changes upon E12 binding to E1. Functional studies suggest that E1(CTD) N-terminal extension (Asp545-Arg562) and the small subunit E12 play an essential role in the binding process of SAM. Structural comparison of the AlphaFold2-predicted E1, E1(CTD)-E12 complex, and the homologous D1-D12 complex of vaccinia virus (VACV) indicates an allosteric activating effect of E1 in MPXV. Our findings provide the structural basis for the MTase activity stimulation of the E1-E12 complex and suggest a potential interface for screening the anti-poxvirus inhibitors. | ||
| - | + | Structural basis of the monkeypox virus mRNA cap N7 methyltransferase complex.,Chen A, Fang N, Zhang Z, Wen Y, Shen Y, Zhang Y, Zhang L, Zhao G, Ding J, Li J Emerg Microbes Infect. 2024 Dec;13(1):2369193. doi: , 10.1080/22221751.2024.2369193. Epub 2024 Jun 27. PMID:38873898<ref>PMID:38873898</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Chen | + | <div class="pdbe-citations 8ze4" style="background-color:#fffaf0;"></div> |
| - | [[Category: Li | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Monkeypox virus]] | ||
| + | [[Category: Chen Ak]] | ||
| + | [[Category: Li JX]] | ||
Current revision
MPXV mRNA cap N7 methyltransferase mutant-H122D
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