4z4p

From Proteopedia

(Difference between revisions)

Revision as of 11:16, 9 September 2015

Structure of the MLL4 SET Domain

Structural highlights

4z4p is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[KMT2D_HUMAN] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[KMT2D_HUMAN] Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Methylation of histone H3 lysine-4 is a hallmark of chromatin associated with active gene expression. The activity of H3K4-specific modification enzymes, in higher eukaryotes the MLL (or KMT2) family, is tightly regulated. The MLL family has six members, each with a specialized function. All contain a catalytic SET domain that associates with a core multiprotein complex for activation. These SET domains segregate into three classes that correlate with the arrangement of targeting domains that populate the rest of the protein. Here we show that, unlike MLL1, the MLL4 SET domain retains significant activity without the core complex. We also present the crystal structure of an inactive MLL4-tagged SET domain construct and describe conformational changes that account for MLL4 intrinsic activity. Finally, our structure explains how the MLL SET domains are able to add multiple methyl groups to the target lysine, despite having the sequence characteristics of a classical monomethylase.

Evolving Catalytic Properties of the MLL Family SET Domain.,Zhang Y, Mittal A, Reid J, Reich S, Gamblin SJ, Wilson JR Structure. 2015 Aug 27. pii: S0969-2126(15)00324-X. doi:, 10.1016/j.str.2015.07.018. PMID:26320581^[4]

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

References

↑ Mo R, Rao SM, Zhu YJ. Identification of the MLL2 complex as a coactivator for estrogen receptor alpha. J Biol Chem. 2006 Jun 9;281(23):15714-20. Epub 2006 Apr 7. PMID:16603732 doi:http://dx.doi.org/M513245200
↑ Cho YW, Hong T, Hong S, Guo H, Yu H, Kim D, Guszczynski T, Dressler GR, Copeland TD, Kalkum M, Ge K. PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J Biol Chem. 2007 Jul 13;282(28):20395-406. Epub 2007 May 11. PMID:17500065 doi:http://dx.doi.org/M701574200
↑ Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11;449(7163):689-94. Epub 2007 Sep 12. PMID:17851529 doi:http://dx.doi.org/10.1038/nature06192
↑ Zhang Y, Mittal A, Reid J, Reich S, Gamblin SJ, Wilson JR. Evolving Catalytic Properties of the MLL Family SET Domain. Structure. 2015 Aug 27. pii: S0969-2126(15)00324-X. doi:, 10.1016/j.str.2015.07.018. PMID:26320581 doi:http://dx.doi.org/10.1016/j.str.2015.07.018

1 Structural highlights
2 Disease
3 Function
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/4z4p"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Structure of the MLL4 SET Domain==
+<StructureSection load='4z4p' size='340' side='right' caption='[[4z4p]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4z4p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z4P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z4P FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=4z4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z4p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4z4p RCSB], [http://www.ebi.ac.uk/pdbsum/4z4p PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.<ref>PMID:16603732</ref> <ref>PMID:17500065</ref> <ref>PMID:17851529</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Methylation of histone H3 lysine-4 is a hallmark of chromatin associated with active gene expression. The activity of H3K4-specific modification enzymes, in higher eukaryotes the MLL (or KMT2) family, is tightly regulated. The MLL family has six members, each with a specialized function. All contain a catalytic SET domain that associates with a core multiprotein complex for activation. These SET domains segregate into three classes that correlate with the arrangement of targeting domains that populate the rest of the protein. Here we show that, unlike MLL1, the MLL4 SET domain retains significant activity without the core complex. We also present the crystal structure of an inactive MLL4-tagged SET domain construct and describe conformational changes that account for MLL4 intrinsic activity. Finally, our structure explains how the MLL SET domains are able to add multiple methyl groups to the target lysine, despite having the sequence characteristics of a classical monomethylase.
-The entry 4z4p is ON HOLD
+Evolving Catalytic Properties of the MLL Family SET Domain.,Zhang Y, Mittal A, Reid J, Reich S, Gamblin SJ, Wilson JR Structure. 2015 Aug 27. pii: S0969-2126(15)00324-X. doi:, 10.1016/j.str.2015.07.018. PMID:26320581<ref>PMID:26320581</ref>
-Authors: Zhang, Z., Mittal, A., Reid, J., Reich, S., Gamblin, S.J., Wilson, J.R.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Histone-lysine N-methyltransferase]]
+[[Category: Gamblin, S J]]
+[[Category: Mittal, A]]
 [[Category: Reich, S]]
+[[Category: Reid, J]]
+[[Category: Wilson, J R]]
 [[Category: Zhang, Z]]
-[[Category: Mittal, A]]
+[[Category: Set domain methyltransferase]]
-[[Category: Wilson, J.R]]
+[[Category: Transferase]]
-[[Category: Reid, J]]
-[[Category: Gamblin, S.J]]

4z4p

From Proteopedia

Revision as of 11:16, 9 September 2015

Structure of the MLL4 SET Domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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