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 and the other half with acidic residues. The structure shows the catalytic subunit or guanylyltransferase which contains the active site that binds the GTP via two motifs rich in basic residues.

3D structures of mRNA capping enzyme

4ckb - 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

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Michal Harel, Alexander Berchansky