8dd5: Difference between revisions

Revision as of 05:40, 5 July 2023

Crystal structure of KAT6A in complex with inhibitor CTx-648 (PF-9363)

Structural highlights

8dd5 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 2.58Å
Ligands:	ALY, R7L, ZN
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]

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8dd5 is ON HOLD  until Paper Publication
+==Crystal structure of KAT6A in complex with inhibitor CTx-648 (PF-9363)==
+<StructureSection load='8dd5' size='340' side='right'caption='[[8dd5]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
-Authors: Greasley, S.E., Johnson, E., Brodsky, O.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8dd5]] 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=8DD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DD5 FirstGlance]. <br>
-Description: Crystal structure of KAT6A in complex with inhibitor CTx-648 (PF-9363)
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.58&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=R7L:2,6-dimethoxy-N-{4-methoxy-6-[(1H-pyrazol-1-yl)methyl]-1,2-benzoxazol-3-yl}benzene-1-sulfonamide'>R7L</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-[[Category: Brodsky, O]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dd5 OCA], [https://pdbe.org/8dd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dd5 RCSB], [https://www.ebi.ac.uk/pdbsum/8dd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dd5 ProSAT]</span></td></tr>
-[[Category: Greasley, S.E]]
+</table>
-[[Category: Johnson, E]]
+== Disease ==
+[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 ==
+[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>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Brodsky O]]
+[[Category: Greasley SE]]
+[[Category: Johnson E]]

8dd5: Difference between revisions

Revision as of 05:40, 5 July 2023

Crystal structure of KAT6A in complex with inhibitor CTx-648 (PF-9363)

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools