2rc4: Difference between revisions

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<StructureSection load='2rc4' size='340' side='right'caption='[[2rc4]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='2rc4' size='340' side='right'caption='[[2rc4]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2rc4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RC4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2rc4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RC4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYST3, MOZ, RUNXBP2, ZNF220 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2rc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rc4 OCA], [http://pdbe.org/2rc4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rc4 RCSB], [http://www.ebi.ac.uk/pdbsum/2rc4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rc4 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rc4 OCA], [https://pdbe.org/2rc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rc4 RCSB], [https://www.ebi.ac.uk/pdbsum/2rc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rc4 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN]] Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP; translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.  Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein.  
[https://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN] Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP; translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.  Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN]] Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2.<ref>PMID:11742995</ref> <ref>PMID:11965546</ref> <ref>PMID:12771199</ref> <ref>PMID:16387653</ref> <ref>PMID:17925393</ref>
[https://www.uniprot.org/uniprot/KAT6A_HUMAN KAT6A_HUMAN] Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2.<ref>PMID:11742995</ref> <ref>PMID:11965546</ref> <ref>PMID:12771199</ref> <ref>PMID:16387653</ref> <ref>PMID:17925393</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2rc4 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2rc4 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human monocytic leukemia zinc finger (MOZ) protein is an essential transcriptional coactivator and histone acetyltransferase (HAT) that plays a primary role in the differentiation of erythroid and myeloid cells and is required to maintain hematopoietic stem cells. Chromosomal translocations involving the HAT-encoded region are also associated with acute myeloid leukemia. Here we present the x-ray crystal structure of the MOZ HAT domain and related biochemical studies. We find that the HAT domain contains a central region that is structurally and functionally conserved with the yeast MYST HAT protein Esa1, but contains more divergent N- and C-terminal regions harboring a TFIIIA-type zinc finger and helix-turn-helix DNA-binding motifs. Solution DNA-binding and acetyltransferase activity assays, in concert with mutagenesis, confirm that the MOZ HAT domain binds strongly to DNA through the zinc finger and helix-turn-helix motifs and that DNA binding and catalysis are not mutually exclusive. Consistent with the DNA-binding properties of MOZ, we also show that MOZ is able to acetylate nucleosomes and free histones equally well, whereas other HATs prefer free histones. Our results reveal, for the first time, that enzymatic and DNA-targeting activities can be contained within the same chromatin regulatory domain.
The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting.,Holbert MA, Sikorski T, Carten J, Snowflack D, Hodawadekar S, Marmorstein R J Biol Chem. 2007 Dec 14;282(50):36603-13. Epub 2007 Oct 9. PMID:17925393<ref>PMID:17925393</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2rc4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Histone acetyltransferase|Histone acetyltransferase]]
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Holbert, M A]]
[[Category: Holbert MA]]
[[Category: Marmorstein, R]]
[[Category: Marmorstein R]]
[[Category: Sikorski, T]]
[[Category: Sikorski T]]
[[Category: Snowflack, D]]
[[Category: Snowflack D]]
[[Category: Activator]]
[[Category: Acyltransferase]]
[[Category: Chromatin regulator]]
[[Category: Coenzyme a binding domain]]
[[Category: Helix-turn-helix]]
[[Category: Metal-binding]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Proto-oncogene]]
[[Category: Repressor]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Transferase]]
[[Category: Zinc-finger]]

Latest revision as of 12:21, 21 February 2024

Crystal Structure of the HAT domain of the human MOZ proteinCrystal Structure of the HAT domain of the human MOZ protein

Structural highlights

2rc4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KAT6A_HUMAN Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP; translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein.

Function

KAT6A_HUMAN Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2.[1] [2] [3] [4] [5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M. Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. EMBO J. 2001 Dec 17;20(24):7184-96. PMID:11742995 doi:10.1093/emboj/20.24.7184
  2. ↑ Pelletier N, Champagne N, Stifani S, Yang XJ. MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene. 2002 Apr 18;21(17):2729-40. PMID:11965546 doi:10.1038/sj.onc.1205367
  3. ↑ Bristow CA, Shore P. Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. Nucleic Acids Res. 2003 Jun 1;31(11):2735-44. PMID:12771199
  4. ↑ Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. PMID:16387653 doi:10.1016/j.molcel.2005.12.007
  5. ↑ Holbert MA, Sikorski T, Carten J, Snowflack D, Hodawadekar S, Marmorstein R. The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting. J Biol Chem. 2007 Dec 14;282(50):36603-13. Epub 2007 Oct 9. PMID:17925393 doi:10.1074/jbc.M705812200

2rc4, resolution 3.00Å

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