6ynn - Revision history

OCA at 13:31, 24 January 2024

2024-01-24T13:31:19Z

←Older revision		Revision as of 13:31, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6ynn' size='340' side='right'caption='[[6ynn]], [[Resolution\|resolution]] 1.20Å' scene=''>		<StructureSection load='6ynn' size='340' side='right'caption='[[6ynn]], [[Resolution\|resolution]] 1.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ynn]] 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=6YNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YNN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ynn]] is a 2 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=6YNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YNN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P0B:6-[[(2-chloranyl-6-fluoranyl-phenyl)methyl-methyl-amino]methyl]-1~{H}-pyrimidine-2,4-dione'>P0B</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P0B:6-[[(2-chloranyl-6-fluoranyl-phenyl)methyl-methyl-amino]methyl]-1~{H}-pyrimidine-2,4-dione'>P0B</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ynn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ynn OCA], [https://pdbe.org/6ynn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ynn RCSB], [https://www.ebi.ac.uk/pdbsum/6ynn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ynn 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=6ynn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ynn OCA], [https://pdbe.org/6ynn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ynn RCSB], [https://www.ebi.ac.uk/pdbsum/6ynn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ynn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/YTDC1_HUMAN YTDC1_HUMAN]] RNA-binding protein that regulates alternative splice site selection.<ref>PMID:20167602</ref>	+	[https://www.uniprot.org/uniprot/YTDC1_HUMAN YTDC1_HUMAN] RNA-binding protein that regulates alternative splice site selection.<ref>PMID:20167602</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bedi~~, R K~~]]	+	[[Category: Bedi RK]]
-	[[Category: Caflisch, A]]	+	[[Category: Caflisch A]]
-	[[Category: Huang, D]]	+	[[Category: Huang D]]
-	[[Category: Wiedmer, L]]	+	[[Category: Wiedmer L]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: M6a]]~~	+
-	~~[[Category: Rna binding protein]]~~	+
-	~~[[Category: Ythdc1~~]]	+

OCA at 10:44, 31 March 2021

2021-03-31T10:44:58Z

←Older revision		Revision as of 10:44, 31 March 2021
Line 1:		Line 1:

	==Crystal structure of YTHDC1 with compound DHU_DC1_135==		==Crystal structure of YTHDC1 with compound DHU_DC1_135==
-	<StructureSection load='6ynn' size='340' side='right'caption='[[6ynn]]' scene=''>	+	<StructureSection load='6ynn' size='340' side='right'caption='[[6ynn]], [[Resolution\|resolution]] 1.20Å' 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=6YNN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YNN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ynn]] 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=6YNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YNN FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6ynn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ynn OCA], [~~http~~://pdbe.org/6ynn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ynn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ynn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ynn 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=P0B:6-[[(2-chloranyl-6-fluoranyl-phenyl)methyl-methyl-amino]methyl]-1~{H}-pyrimidine-2,4-dione'>P0B</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ynn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ynn OCA], [https://pdbe.org/6ynn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ynn RCSB], [https://www.ebi.ac.uk/pdbsum/6ynn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ynn ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/YTDC1_HUMAN YTDC1_HUMAN]] RNA-binding protein that regulates alternative splice site selection.<ref>PMID:20167602</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	N6-Methyladenosine (m(6)A) is the most frequent modification in eukaryotic messenger RNA (mRNA) and its cellular processing and functions are regulated by the reader proteins YTHDCs and YTHDFs. However, the mechanism of m(6)A recognition by the reader proteins is still elusive. Here, we investigate this recognition process by combining atomistic simulations, site-directed mutagenesis, and biophysical experiments using YTHDC1 as a model. We find that the N6 methyl group of m(6)A contributes to the binding through its specific interactions with an aromatic cage (formed by Trp377 and Trp428) and also by favoring the association-prone conformation of m(6)A-containing RNA in solution. The m(6)A binding site dynamically equilibrates between multiple metastable conformations with four residues being involved in the regulation of m(6)A binding (Trp428, Met438, Ser378, and Thr379). Trp428 switches between two conformational states to build and dismantle the aromatic cage. Interestingly, mutating Met438 and Ser378 to alanine does not alter m(6)A binding to the protein but significantly redistributes the binding enthalpy and entropy terms, i.e., enthalpy-entropy compensation. Such compensation is reasoned by different entropy-enthalpy transduction associated with both conformational changes of the wild-type and mutant proteins and the redistribution of water molecules. In contrast, the point mutant Thr379Val significantly changes the thermal stability and binding capability of YTHDC1 to its natural ligand. Additionally, thermodynamic analysis and free energy calculations shed light on the role of a structural water molecule that synergistically binds to YTHDC1 with m(6)A and acts as the hub of a hydrogen-bond network. Taken together, the experimental data and simulation results may accelerate the discovery of chemical probes, m(6)A-editing tools, and drug candidates against reader proteins.
		+
		+	Atomistic and Thermodynamic Analysis of N6-Methyladenosine (m(6)A) Recognition by the Reader Domain of YTHDC1.,Li Y, Bedi RK, Wiedmer L, Sun X, Huang D, Caflisch A J Chem Theory Comput. 2021 Feb 9;17(2):1240-1249. doi: 10.1021/acs.jctc.0c01136. , Epub 2021 Jan 20. PMID:33472367<ref>PMID:33472367</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ynn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bedi RK]]	+	[[Category: Bedi, R K]]
-	[[Category: Caflisch A]]	+	[[Category: Caflisch, A]]
-	[[Category: Huang D]]	+	[[Category: Huang, D]]
-	[[Category: Wiedmer L]]	+	[[Category: Wiedmer, L]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: M6a]]
		+	[[Category: Rna binding protein]]
		+	[[Category: Ythdc1]]

OCA at 06:02, 20 January 2021

2021-01-20T06:02:41Z

←Older revision		Revision as of 06:02, 20 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ynn ~~is ON HOLD~~	+	==Crystal structure of YTHDC1 with compound DHU_DC1_135==
-		+	<StructureSection load='6ynn' size='340' side='right'caption='[[6ynn]]' scene=''>
-	~~Authors~~: ~~Bedi~~, R.K., ~~Huang~~, D., ~~Wiedmer, L~~., ~~Caflisch, A~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YNN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YNN FirstGlance]. <br>
-	~~Description: Crystal structure of YTHDC1 with compound DHU_DC1_135~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ynn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ynn OCA], [http://pdbe.org/6ynn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ynn RCSB], [http://www.ebi.ac.uk/pdbsum/6ynn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ynn ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Caflisch, A~~]]	+	__TOC__
-	[[Category: ~~Bedi, R.K~~]]	+	</StructureSection>
-	[[Category: ~~Wiedmer, L~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Huang, D~~]]	+	[[Category: Bedi RK]]
		+	[[Category: Caflisch A]]
		+	[[Category: Huang D]]
		+	[[Category: Wiedmer L]]

OCA: Protected "6ynn" [edit=sysop:move=sysop]

2020-04-22T04:24:35Z

Protected "6ynn" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:24, 22 April 2020

OCA: New page: '''Unreleased structure''' The entry 6ynn is ON HOLD Authors: Bedi, R.K., Huang, D., Wiedmer, L., Caflisch, A. Description: Crystal structure of YTHDC1 with compound DHU_DC1_135 [[Cate...

2020-04-22T04:24:33Z

New page: '''Unreleased structure''' The entry 6ynn is ON HOLD Authors: Bedi, R.K., Huang, D., Wiedmer, L., Caflisch, A. Description: Crystal structure of YTHDC1 with compound DHU_DC1_135 [[Cate...

New page

'''Unreleased structure'''

The entry 6ynn is ON HOLD

Authors: Bedi, R.K., Huang, D., Wiedmer, L., Caflisch, A.

Description: Crystal structure of YTHDC1 with compound DHU_DC1_135
[[Category: Unreleased Structures]]
[[Category: Caflisch, A]]
[[Category: Bedi, R.K]]
[[Category: Wiedmer, L]]
[[Category: Huang, D]]