OCA at 20:16, 20 October 2021

OCA — Wed, 20 Oct 2021 20:16:15 GMT

←Older revision		Revision as of 20:16, 20 October 2021
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	==Human ATM kinase with bound inhibitor KU-55933==		==Human ATM kinase with bound inhibitor KU-55933==
-	<StructureSection load='7ni5' size='340' side='right'caption='[[7ni5]]' scene=''>	+	<StructureSection load='7ni5' size='340' side='right'caption='[[7ni5]], [[Resolution\|resolution]] 2.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NI5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ni5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NI5 FirstGlance]. <br>
-	</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=7ni5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ni5 OCA], [https://pdbe.org/7ni5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ni5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ni5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ni5 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UF8:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one'>UF8</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7ni4\|7ni4]]</div></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ATM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7ni5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ni5 OCA], [https://pdbe.org/7ni5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ni5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ni5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ni5 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/ATM_HUMAN ATM_HUMAN]] Mantle cell lymphoma;B-cell chronic lymphocytic leukemia;Combined cervical dystonia;Ataxia-telangiectasia;Ataxia-telangiectasia variant. The disease is caused by mutations affecting the gene represented in this entry. Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients.<ref>PMID:9288106</ref> <ref>PMID:9334731</ref> <ref>PMID:9463314</ref> <ref>PMID:9488043</ref> <ref>PMID:9573030</ref> Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL).<ref>PMID:10397742</ref> <ref>PMID:10706620</ref> <ref>PMID:9288106</ref> Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B-lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.<ref>PMID:10023947</ref> <ref>PMID:10397742</ref> <ref>PMID:9892178</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/ATM_HUMAN ATM_HUMAN]] Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response.<ref>PMID:10973490</ref> <ref>PMID:12556884</ref> <ref>PMID:14871926</ref> <ref>PMID:15916964</ref> <ref>PMID:16086026</ref> <ref>PMID:16858402</ref> <ref>PMID:17923702</ref> <ref>PMID:19965871</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human checkpoint kinase ataxia telangiectasia-mutated (ATM) plays a key role in initiation of the DNA damage response following DNA double-strand breaks. ATM inhibition is a promising approach in cancer therapy, but, so far, detailed insights into the binding modes of known ATM inhibitors have been hampered due to the lack of high-resolution ATM structures. Using cryo-EM, we have determined the structure of human ATM to an overall resolution sufficient to build a near-complete atomic model and identify two hitherto unknown zinc-binding motifs. We determined the structure of the kinase domain bound to ATPgammaS and to the ATM inhibitors KU-55933 and M4076 at 2.8 A, 2.8 A and 3.0 A resolution, respectively. The mode of action and selectivity of the ATM inhibitors can be explained by structural comparison and provide a framework for structure-based drug design.
		+
		+	Molecular basis of human ATM kinase inhibition.,Stakyte K, Rotheneder M, Lammens K, Bartho JD, Gradler U, Fuchss T, Pehl U, Alt A, van de Logt E, Hopfner KP Nat Struct Mol Biol. 2021 Sep 23. pii: 10.1038/s41594-021-00654-x. doi:, 10.1038/s41594-021-00654-x. PMID:34556870<ref>PMID:34556870</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ni5" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bartho JD]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Hopfner KP]]	+	[[Category: Bartho, J D]]
-	[[Category: Lammens K]]	+	[[Category: Hopfner, K P]]
-	[[Category: Rotheneder M]]	+	[[Category: Lammens, K]]
-	[[Category: Stakyte K]]	+	[[Category: Rotheneder, M]]
		+	[[Category: Stakyte, K]]
		+	[[Category: Cancer research]]
		+	[[Category: Dna damage response]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Signaling protein]]

OCA at 05:55, 6 October 2021

OCA — Wed, 06 Oct 2021 05:55:15 GMT

←Older revision		Revision as of 05:55, 6 October 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7ni5 is ~~ON HOLD until Paper Publication~~	+	==Human ATM kinase with bound inhibitor KU-55933==
-		+	<StructureSection load='7ni5' size='340' side='right'caption='[[7ni5]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NI5 FirstGlance]. <br>
-	~~Description~~:	+	</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=7ni5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ni5 OCA], [https://pdbe.org/7ni5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ni5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ni5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ni5 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bartho JD]]
		+	[[Category: Hopfner KP]]
		+	[[Category: Lammens K]]
		+	[[Category: Rotheneder M]]
		+	[[Category: Stakyte K]]

OCA at 05:36, 24 March 2021

OCA — Wed, 24 Mar 2021 05:36:25 GMT

←Older revision		Revision as of 05:36, 24 March 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ni5 is ON HOLD	+	The entry 7ni5 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7ni5" [edit=sysop:move=sysop]

OCA — Wed, 17 Feb 2021 08:58:09 GMT

Protected "7ni5" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:58, 17 February 2021

OCA: New page: '''Unreleased structure''' The entry 7ni5 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Feb 2021 08:58:09 GMT

New page: '''Unreleased structure''' The entry 7ni5 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7ni5 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7ni5 - Revision history

OCA at 20:16, 20 October 2021

OCA at 05:55, 6 October 2021

OCA at 05:36, 24 March 2021

OCA: Protected "7ni5" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7ni5 is ON HOLD Authors: Description: Category: Unreleased Structures