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MRNA capping enzyme
From Proteopedia
(Difference between revisions)
(New page: <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref>...) |
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| - | <StructureSection load=' | + | <StructureSection load='4ckb' size='400' side='right' caption='Vaccinia virus mRNA capping enzyme catalytic subunit (pink) and regulatory subunit (yellow) complex with SAH and GTP (PDB code [[4ckb]])' scene='84/844924/Cv/3'> |
| - | + | __TOC__ | |
== Function == | == Function == | ||
| - | '''mRNA capping enzyme''' (Mce) | + | '''mRNA capping enzyme''' (Mce) is a multifunctional protein with RNA triphosphatase, RNA guanylyltransferase, RNA methyltransferase and transcription factor activities. The 5' cap of mRNA is required for its stability and efficient translation. Mce activity entails the transfer of GMP from GTP to the 5'-diphosphate end of mRNA via a enzyme-(lysyl-GMP) intermediate by RNA triphosphatase and RNA guanylyltransferaseand finally the GpppRNA is converted to m7GpppRNA by RNA methyltransferase. In Vaccinia virus the active site is at Lys260 within the conserved motif KxDG in the catalytic subunit<ref>PMID:7565775</ref>. |
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== Relevance == | == Relevance == | ||
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| + | Inhibition of Mce may provide a route for selecting therapeutic targeting of cancer cells which acquired deregulated c-Myc which is a potent driver of many human cancers<ref>PMID:27756891</ref> | ||
== Structural highlights == | == Structural highlights == | ||
| - | + | <scene name='84/844924/Cv/14'>Vaccinia virus mRNA capping enzyme catalytic subunit and regulatory subunit complex with SAH and GTP</scene> (PDB code [[4ckb]]). The 3D structure of Vaccinia virus Mce shows the regulatory subunit or RNA triphosphatase domain which forms a hydrophilic tunnel. The <scene name='84/844924/Cv/15'>tunnel is lined with charged residues with one half of the internal surface is lined almost exclusively with basic residues (colored in royalblue) and the other half with acidic residues (colored in red)</scene>. The structure shows the catalytic subunit or guanylyltransferase which contains the active site that binds the GTP via <scene name='84/844924/Cv/16'>two motifs</scene> rich in basic residues<ref>PMID:24607143</ref>. | |
| - | </ | + | *<scene name='84/844924/Cv/17'>Whole GTP binding site</scene>. Water molecule is shown as red sphere. |
| + | *<scene name='84/844924/Cv/18'>Basic residues</scene> (colored in royalblue), which are situated in GTP-binding site. | ||
| + | *<scene name='84/844924/Cv/12'>SAH binding site</scene>. | ||
| + | *<scene name='84/844924/Cv/13'>Stacking interaction between Tyr residue and SAH</scene>. | ||
==3D structures of mRNA capping enzyme== | ==3D structures of mRNA capping enzyme== | ||
| + | [[mRNA capping enzyme 3D structures]] | ||
| - | [[2c46]] - hMce TPase domain 1-219 - human<br /> | ||
| - | [[3s24]] - hMce GTase domain 229-567 <br /> | ||
| - | [[1i9t]], [[1i9s]] - mMce TPase domain - mouse<br /> | ||
| - | [[3rtx]] - mMce GTase domain + DNA-dependent RNA polymerase II C-terminal + guanine<br /> | ||
| - | [[3kyh]] - yMce α+β subunits - yeast<br /> | ||
| - | [[4pz7]] - fyMce α subunit - fission yeast<br /> | ||
| - | [[4pz8]] - fyMce α subunit + SPT5<br /> | ||
| - | [[4pz6]] - fyMce α subunit + DNA-dependent RNA polymerase II C terminal + GMP<br /> | ||
| - | [[4pn0]] - fyMce β subunit<br /> | ||
| - | [[4pn1]] - fyMce β subunit + SPT5 peptide<br /> | ||
| - | [[1p16]] - Mce α subunit + GTP + RNA polymerase peptide - Candida albicans<br /> | ||
| - | [[1ri5]] - EcMce - Encephalitozoon cuniculi<br /> | ||
| - | [[1ri4]] - EcMce + SAM<br /> | ||
| - | [[1z3c]] - EcMce + SAM derivative<br /> | ||
| - | [[1ri3]] - EcMce + SAH<br /> | ||
| - | [[1ri2]] - EcMce + GTG<br /> | ||
| - | [[1ri1]] - EcMce + SAH + GTG<br /> | ||
| - | [[1ckn]], [[1ckm]] - PbcvMce + GTP - Paramecium bursaria chlorella virus<br /> | ||
| - | [[1cko]] - PbcvMce + GPPPG<br /> | ||
| - | [[4cke]], [[4ckc]], [[2vdw]] - VvMce catalytic+regulatory subunits + SAH - Vaccinia virus<br /> | ||
| - | [[4ckb]] - VvMce catalytic+regulatory subunits + GTP + SAH<br /> | ||
| - | [[6rfl]] - VvMce catalytic+regulatory subunits + DNA-dependent RNA polymerase - Cryo EM<br /> | ||
| - | [[6rie]] - VvMce catalytic+regulatory subunits + DNA-dependent RNA polymerase + GDP + SAM - Cryo EM<br /> | ||
| - | [[5x6x]] - RdvMce - Rice dwarf virus<br /> | ||
| - | [[5x6z]] - RdvMce + GTP + GDP<br /> | ||
| - | [[5x71]] - RdvMce + 5GP<br /> | ||
| - | [[5x6y]] - RdvMce + SAM<br /> | ||
| - | [[5x70]] - RdvMce + RNA<br /> | ||
== References == | == References == | ||
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<references/> | <references/> | ||
| + | </StructureSection> | ||
| + | [[Category:Topic Page]] | ||
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