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MRNA capping enzyme

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Vaccinia virus mRNA capping enzyme catalytic subunit (pink) and regulatory subunit (yellow) complex with SAH and GTP (PDB code 4ckb)

Drag the structure with the mouse to rotate

1 Function
2 Relevance
3 Structural highlights
4 3D structures of mRNA capping enzyme
5 References

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^[1].

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^[2]

Structural highlights

(PDB code 4ckb). The 3D structure of Vaccinia virus Mce shows the regulatory subunit or RNA triphosphatase domain which forms a hydrophilic tunnel. The . The structure shows the catalytic subunit or guanylyltransferase which contains the active site that binds the GTP via rich in basic residues^[3].

. Water molecule is shown as red sphere.
(colored in royalblue), which are situated in GTP-binding site.
.
.

3D structures of mRNA capping enzyme

mRNA capping enzyme 3D structures

References

↑ Cong P, Shuman S. Mutational analysis of mRNA capping enzyme identifies amino acids involved in GTP binding, enzyme-guanylate formation, and GMP transfer to RNA. Mol Cell Biol. 1995 Nov;15(11):6222-31. doi: 10.1128/mcb.15.11.6222. PMID:7565775 doi:http://dx.doi.org/10.1128/mcb.15.11.6222
↑ Lombardi O, Varshney D, Phillips NM, Cowling VH. c-Myc deregulation induces mRNA capping enzyme dependency. Oncotarget. 2016 Dec 13;7(50):82273-82288. doi: 10.18632/oncotarget.12701. PMID:27756891 doi:http://dx.doi.org/10.18632/oncotarget.12701
↑ Kyrieleis OJ, Chang J, de la Pena M, Shuman S, Cusack S. Crystal structure of vaccinia virus mRNA capping enzyme provides insights into the mechanism and evolution of the capping apparatus. Structure. 2014 Mar 4;22(3):452-65. doi: 10.1016/j.str.2013.12.014. PMID:24607143 doi:http://dx.doi.org/10.1016/j.str.2013.12.014