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3gdh

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Revision as of 22:22, 24 December 2014

Methyltransferase domain of human Trimethylguanosine Synthase 1 (TGS1) bound to m7GTP and adenosyl-homocysteine (active form)

Structural highlights

3gdh is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	TGS1, HCA137, NCOA6IP, PIMT (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 PubMed

The 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

↑ Zhu Y, Qi C, Cao WQ, Yeldandi AV, Rao MS, Reddy JK. Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10380-5. Epub 2001 Aug 21. PMID:11517327 doi:http://dx.doi.org/10.1073/pnas.181347498
↑ Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK. Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation. J Biol Chem. 2002 May 31;277(22):20011-9. Epub 2002 Mar 23. PMID:11912212 doi:http://dx.doi.org/10.1074/jbc.M201739200
↑ Lemm I, Girard C, Kuhn AN, Watkins NJ, Schneider M, Bordonne R, Luhrmann R. Ongoing U snRNP biogenesis is required for the integrity of Cajal bodies. Mol Biol Cell. 2006 Jul;17(7):3221-31. Epub 2006 May 10. PMID:16687569 doi:http://dx.doi.org/10.1091/mbc.E06-03-0247
↑ Hausmann S, Zheng S, Costanzo M, Brost RL, Garcin D, Boone C, Shuman S, Schwer B. Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways. J Biol Chem. 2008 Nov 14;283(46):31706-18. doi: 10.1074/jbc.M806127200. Epub 2008, Sep 5. PMID:18775984 doi:http://dx.doi.org/10.1074/jbc.M806127200
↑ Monecke T, Dickmanns A, Ficner R. Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1. Nucleic Acids Res. 2009 Jul;37(12):3865-77. Epub 2009 Apr 22. PMID:19386620 doi:10.1093/nar/gkp249

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gdh"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gdh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gdh RCSB], [http://www.ebi.ac.uk/pdbsum/3gdh PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TGS1_HUMAN 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.<ref>PMID:11517327</ref> <ref>PMID:11912212</ref> <ref>PMID:16687569</ref> <ref>PMID:18775984</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3gdh

From Proteopedia

Revision as of 22:22, 24 December 2014

Methyltransferase domain of human Trimethylguanosine Synthase 1 (TGS1) bound to m7GTP and adenosyl-homocysteine (active form)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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