6d2l: Difference between revisions

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'''Unreleased structure'''


The entry 6d2l is ON HOLD
==Crystal structure of human CARM1 with (S)-SKI-72==
 
<StructureSection load='6d2l' size='340' side='right' caption='[[6d2l]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
Authors: DONG, A., ZENG, H., WALKER, J.R., Hutchinson, A., Seitova, A., LUO, M., CAI, X.C., KE, W., WANG, J., SHI, C., ZHENG, W., LEE, J.P., IBANEZ, G., Bountra, C., Arrowsmith, C.H., Edwards, A.M., BROWN, P.J., WU, H., Structural Genomics Consortium (SGC)
== Structural highlights ==
 
<table><tr><td colspan='2'>[[6d2l]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D2L FirstGlance]. <br>
Description: Crystal structure of human CARM1 with (S)-SKI-72
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTG:(2S,5S)-2-amino-6-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]-5-[(benzylamino)methyl]-N-[2-(4-hydroxyphenyl)ethyl]hexanamide'>FTG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
[[Category: Unreleased Structures]]
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Type_I_protein_arginine_methyltransferase Type I protein arginine methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.319 2.1.1.319] </span></td></tr>
<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=6d2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d2l OCA], [http://pdbe.org/6d2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d2l RCSB], [http://www.ebi.ac.uk/pdbsum/6d2l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d2l ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CARM1_HUMAN CARM1_HUMAN]] Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.<ref>PMID:16497732</ref> <ref>PMID:19405910</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Type I protein arginine methyltransferase]]
[[Category: Arrowsmith, C H]]
[[Category: BROWN, P J]]
[[Category: Bountra, C]]
[[Category: CAI, X C]]
[[Category: DONG, A]]
[[Category: Edwards, A M]]
[[Category: Hutchinson, A]]
[[Category: Hutchinson, A]]
[[Category: Ke, W]]
[[Category: IBANEZ, G]]
[[Category: Ibanez, G]]
[[Category: KE, W]]
[[Category: Arrowsmith, C.H]]
[[Category: LEE, J P]]
[[Category: LUO, M]]
[[Category: Structural genomic]]
[[Category: SHI, C]]
[[Category: Seitova, A]]
[[Category: Seitova, A]]
[[Category: Dong, A]]
[[Category: WALKER, J R]]
[[Category: Lee, J.P]]
[[Category: WANG, J]]
[[Category: Luo, M]]
[[Category: WU, H]]
[[Category: Brown, P.J]]
[[Category: ZENG, H]]
[[Category: Zeng, H]]
[[Category: ZHENG, W]]
[[Category: Shi, C]]
[[Category: Carm1]]
[[Category: Cai, X.C]]
[[Category: Prmt4]]
[[Category: Edwards, A.M]]
[[Category: Sgc]]
[[Category: Walker, J.R]]
[[Category: Ski-72 inhibitor]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Transferase-inhibitor complex]]
[[Category: Wang, J]]
[[Category: Wu, H]]
[[Category: Zheng, W]]
[[Category: Bountra, C]]

Revision as of 10:25, 23 May 2018

Crystal structure of human CARM1 with (S)-SKI-72Crystal structure of human CARM1 with (S)-SKI-72

Structural highlights

6d2l is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , ,
Activity:Type I protein arginine methyltransferase, with EC number 2.1.1.319
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CARM1_HUMAN] Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.[1] [2]

References

  1. ↑ Miao F, Li S, Chavez V, Lanting L, Natarajan R. Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17. Mol Endocrinol. 2006 Jul;20(7):1562-73. Epub 2006 Feb 23. PMID:16497732 doi:me.2005-0365
  2. ↑ Lakowski TM, Frankel A. Kinetic analysis of human protein arginine N-methyltransferase 2: formation of monomethyl- and asymmetric dimethyl-arginine residues on histone H4. Biochem J. 2009 Jun 26;421(2):253-61. doi: 10.1042/BJ20090268. PMID:19405910 doi:10.1042/BJ20090268

6d2l, resolution 2.00Å

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