MRNA capping enzyme

spinqualitylabelsall models Vaccinia virus mRNA capping enzyme catalytic subunit (pink) and regulatory subunit (yellow) complex with SAH and GTP (PDB code 4ckb) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function 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. Relevance 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 Structural highlights Vaccinia virus mRNA capping enzyme catalytic subunit and regulatory subunit complex with SAH and GTP (PDB code 4ckb). The 3D structure of Vaccinia virus Mce shows the regulatory subunit or RNA triphosphatase domain which forms a hydrophilic tunnel. The 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). The structure shows the catalytic subunit or guanylyltransferase which contains the active site that binds the GTP via two motifs rich in basic residues. Whole GTP binding site. Water molecule is shown as red sphere. Basic residues (colored in royalblue), which are situated in GTP-binding site. SAH binding site. Stacking interaction between Tyr residue and SAH. 3D structures of mRNA capping enzyme 2c46 - hMce TPase domain 1-219 - human 3s24 - hMce GTase domain 229-567 1i9t, 1i9s - mMce TPase domain - mouse 3rtx - mMce GTase domain + DNA-dependent RNA polymerase II C-terminal + guanine 3kyh - yMce α+β subunits - yeast 4pz7 - fyMce α subunit - fission yeast 4pz8 - fyMce α subunit + SPT5 4pz6 - fyMce α subunit + DNA-dependent RNA polymerase II C terminal + GMP 4pn0 - fyMce β subunit 4pn1 - fyMce β subunit + SPT5 peptide 1p16 - Mce α subunit + GTP + RNA polymerase peptide - Candida albicans 1ri5 - EcMce - Encephalitozoon cuniculi 1ri4 - EcMce + SAM 1z3c - EcMce + SAM derivative 1ri3 - EcMce + SAH 1ri2 - EcMce + GTG 1ri1 - EcMce + SAH + GTG 1ckn, 1ckm - PbcvMce + GTP - Paramecium bursaria chlorella virus 1cko - PbcvMce + GPPPG 4cke, 4ckc, 2vdw - VvMce catalytic+regulatory subunits + SAH - Vaccinia virus 4ckb - VvMce catalytic+regulatory subunits + GTP + SAH 6rfl - VvMce catalytic+regulatory subunits + DNA-dependent RNA polymerase - Cryo EM 6rie - VvMce catalytic+regulatory subunits + DNA-dependent RNA polymerase + GDP + SAM - Cryo EM 5x6x - RdvMce - Rice dwarf virus 5x6z - RdvMce + GTP + GDP 5x71 - RdvMce + 5GP 5x6y - RdvMce + SAM 5x70 - RdvMce + RNA 8axv - cvMce – chikungunya virus – Cryo EM 8aov - cvMce + GTP – Cryo EM 7fgg - cvMce + 7GMP – Cryo EM 7fgh, 7fgi, 8aow - cvMce + SAH + 7GMP – Cryo EM 7y38 - cvMce + RNA polymerase + ATP + GTP – Cryo EM 7x01 - cvMce + inhibitor – Cryo EM

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