3gdh
From Proteopedia
Methyltransferase domain of human Trimethylguanosine Synthase 1 (TGS1) bound to m7GTP and adenosyl-homocysteine (active form)
Structural highlights
Function[TGS1_HUMAN] Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 5'-cap of spliceosomal small nuclear RNAs, some small nucleolar RNAs and of telomerase RNA was found to be hypermethylated in vivo. The Trimethylguanosine Synthase 1 (TGS1) mediates this conversion of the 7-methylguanosine-cap to the 2,2,7-trimethylguanosine (m(3)G)-cap during maturation of the RNPs. For mammalian UsnRNAs the generated m(2,2,7)G-cap is one part of a bipartite import signal mediating the transport of the UsnRNP-core complex into the nucleus. In order to understand the structural organization of human TGS1 as well as substrate binding and recognition we solved the crystal structure of the active TGS1 methyltransferase domain containing both, the minimal substrate m(7)GTP and the reaction product S-adenosyl-L-homocysteine (AdoHcy). The methyltransferase of human TGS1 harbors the canonical class 1 methyltransferase fold as well as an unique N-terminal, alpha-helical domain of 40 amino acids, which is essential for m(7)G-cap binding and catalysis. The crystal structure of the substrate bound methyltransferase domain as well as mutagenesis studies provide insight into the catalytic mechanism of TGS1. Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1.,Monecke T, Dickmanns A, Ficner R Nucleic Acids Res. 2009 Jul;37(12):3865-77. Epub 2009 Apr 22. PMID:19386620[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Dickmanns, A | Ficner, R | Monecke, T | Cap | Cytoplasm | Dimethyltransferase | M7g | Methyltransferase | Nucleus | Phosphoprotein | Polymorphism | Snorna | Telomerase | Transcription | Transcription regulation | Transferase | Usnrna
