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4c06

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Revision as of 13:16, 13 March 2019

Crystal structure of M. musculus protein arginine methyltransferase PRMT6 with MgCl2

Structural highlights

4c06 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4c03, 4c04, 4c05, 4c07, 4c08
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ANM6_MOUSE] Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator.^[1] ^[2]

Publication Abstract from PubMed

PRMT6 is a protein arginine methyltransferase involved in transcriptional regulation, human immunodeficiency virus pathogenesis, DNA base excision repair, and cell cycle progression. Like other PRMTs, PRMT6 is overexpressed in several cancer types and is therefore considered as a potential anti-cancer drug target. In the present study, we described six crystal structures of PRMT6 from Mus musculus, solved and refined at 1.34A for the highest resolution structure. The crystal structures revealed that the folding of the helix alphaX is required to stabilize a productive active site before methylation of the bound peptide can occur. In the absence of cofactor, metal cations can be found in the catalytic pocket at the expected position of the guanidinium moiety of the target arginine substrate. Using mass spectrometry under native conditions, we show that PRMT6 dimer binds two cofactor and a single H4 peptide molecules. Finally, we characterized a new site of in vitro automethylation of mouse PRMT6 at position 7.

Functional insights from high resolution structures of mouse protein arginine methyltransferase 6.,Bonnefond L, Stojko J, Mailliot J, Troffer-Charlier N, Cura V, Wurtz JM, Cianferani S, Cavarelli J J Struct Biol. 2015 Jun 18. pii: S1047-8477(15)30021-6. doi:, 10.1016/j.jsb.2015.06.017. PMID:26094878^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Neault M, Mallette FA, Vogel G, Michaud-Levesque J, Richard S. Ablation of PRMT6 reveals a role as a negative transcriptional regulator of the p53 tumor suppressor. Nucleic Acids Res. 2012 Oct;40(19):9513-21. doi: 10.1093/nar/gks764. Epub 2012, Aug 16. PMID:22904064 doi:http://dx.doi.org/10.1093/nar/gks764
↑ Han HS, Jung CY, Yoon YS, Choi S, Choi D, Kang G, Park KG, Kim ST, Koo SH. Arginine methylation of CRTC2 is critical in the transcriptional control of hepatic glucose metabolism. Sci Signal. 2014 Feb 25;7(314):ra19. doi: 10.1126/scisignal.2004479. PMID:24570487 doi:http://dx.doi.org/10.1126/scisignal.2004479
↑ Bonnefond L, Stojko J, Mailliot J, Troffer-Charlier N, Cura V, Wurtz JM, Cianferani S, Cavarelli J. Functional insights from high resolution structures of mouse protein arginine methyltransferase 6. J Struct Biol. 2015 Jun 18. pii: S1047-8477(15)30021-6. doi:, 10.1016/j.jsb.2015.06.017. PMID:26094878 doi:http://dx.doi.org/10.1016/j.jsb.2015.06.017

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4c06"

@@ Line 1: / Line 1: @@
 ==Crystal structure of M. musculus protein arginine methyltransferase PRMT6 with MgCl2==
-<StructureSection load='4c06' size='340' side='right' caption='[[4c06]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='4c06' size='340' side='right'caption='[[4c06]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4c06]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C06 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C06 FirstGlance]. <br>
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
 [[Category: Bonnefond, L]]

4c06

From Proteopedia

Revision as of 13:16, 13 March 2019

Crystal structure of M. musculus protein arginine methyltransferase PRMT6 with MgCl2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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