8dqj - Revision history

OCA at 10:13, 25 October 2023

OCA — Wed, 25 Oct 2023 10:13:07 GMT

←Older revision		Revision as of 10:13, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dqj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candidatus_Methanomethylophilus_alvus Candidatus Methanomethylophilus alvus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DQJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dqj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candidatus_Methanomethylophilus_alvus Candidatus Methanomethylophilus alvus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DQJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=T7Q:(2~{S})-2-azanyl-3-(9-oxidanylidene-10~{H}-acridin-2-yl)propanoic+acid'>T7Q</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]] 1.54Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=T7Q:(2~{S})-2-azanyl-3-(9-oxidanylidene-10~{H}-acridin-2-yl)propanoic+acid'>T7Q</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=8dqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dqj OCA], [https://pdbe.org/8dqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dqj RCSB], [https://www.ebi.ac.uk/pdbsum/8dqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dqj 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=8dqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dqj OCA], [https://pdbe.org/8dqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dqj RCSB], [https://www.ebi.ac.uk/pdbsum/8dqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dqj ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:21, 7 December 2022

OCA — Wed, 07 Dec 2022 08:21:02 GMT

←Older revision		Revision as of 08:21, 7 December 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8dqj is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of pyrrolysyl-tRNA synthetase from Methanomethylophilus alvus engineered for acridone amino acid (AST) bound to ATP and acridone==
		+	<StructureSection load='8dqj' size='340' side='right'caption='[[8dqj]], [[Resolution\|resolution]] 1.54Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8dqj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candidatus_Methanomethylophilus_alvus Candidatus Methanomethylophilus alvus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DQJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=T7Q:(2~{S})-2-azanyl-3-(9-oxidanylidene-10~{H}-acridin-2-yl)propanoic+acid'>T7Q</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=8dqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dqj OCA], [https://pdbe.org/8dqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dqj RCSB], [https://www.ebi.ac.uk/pdbsum/8dqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dqj ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A3G3IHP7_9ARCH A0A3G3IHP7_9ARCH]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A recently developed genetic code expansion (GCE) platform based on the pyrrolysine amino-acyl tRNA synthetase (PylRS)/tRNA(Pyl) pair from Methanomethylophilus alvus (Ma) has improved solubility and lower susceptibility to proteolysis compared with the homologous and commonly used Methanosarcina barkeri (Mb) and M. mazei (Mm) PylRS GCE platforms. We recently created two new Ma PylRS variants for the incorporation of the fluorescent amino acid, acridonyl-alanine (Acd), into proteins at amber codons: one based on "transplanting" active site mutations from an established high-efficiency Mb PylRS and one that was de novo selected from a library of mutants. Here, we present the crystal structures of these two Ma PylRS variants with Acd/ATP bound to understand why the "active site transplant" variant (Acd-AST) displayed 6-fold worse Acd incorporation efficiency than the de novo selected PylRS (called Acd-RS1). The structures reveal that the Acd-AST binding pocket is too small and binds the three-ring aromatic Acd in a distorted conformation, whereas the more spacious Acd-RS1 active site binds Acd in a relaxed, planar conformation stabilized by a network of solvent-mediated hydrogen bonds. The poor performance of the AST enzyme is ascribed to a shift in the Ma PylRS beta-sheet framework relative to that of the Mb enzyme. This illustrates a general reason why "active site transplantation" may not succeed in creating efficient Ma PylRSs for other noncanonical amino acids. This work also provides structural details that will help guide the development of future Ma PylRS/tRNA(Pyl) GCE systems via de novo selection or directed evolution methods.

-	~~Authors:~~ Gottfried-Lee, I., Karplus~~, P.A.~~, Mehl, R.A.~~, Cooley, R~~.B.	+	Structures of Methanomethylophilus alvus Pyrrolysine tRNA-Synthetases Support the Need for De Novo Selections When Altering the Substrate Specificity.,Gottfried-Lee I, Perona JJ, Karplus PA, Mehl RA, Cooley RB ACS Chem Biol. 2022 Nov 17. doi: 10.1021/acschembio.2c00640. PMID:36395426<ref>PMID:36395426</ref>

-	~~Description: Crystal structure~~ of ~~pyrrolysyl~~-~~tRNA synthetase from Methanomethylophilus alvus engineered for acridone amino acid (AST) bound to ATP and acridone~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Mehl, R.A~~]]	+	<div class="pdbe-citations 8dqj" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Karplus, P.A~~]]	+	== References ==
-	[[Category: Gottfried-Lee, I]]	+	<references/>
-	[[Category: ~~Cooley, R.B~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Candidatus Methanomethylophilus alvus]]
		+	[[Category: Large Structures]]
		+	[[Category: Cooley RB]]
		+	[[Category: Gottfried-Lee I]]
		+	[[Category: Karplus PA]]
		+	[[Category: Mehl RA]]

OCA at 03:48, 25 August 2022

OCA — Thu, 25 Aug 2022 03:48:41 GMT

←Older revision		Revision as of 03:48, 25 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8dqj is ON HOLD	+	The entry 8dqj is ON HOLD until Paper Publication

	Authors: Gottfried-Lee, I., Karplus, P.A., Mehl, R.A., Cooley, R.B.		Authors: Gottfried-Lee, I., Karplus, P.A., Mehl, R.A., Cooley, R.B.

OCA: Protected "8dqj" [edit=sysop:move=sysop]

OCA — Wed, 27 Jul 2022 16:46:41 GMT

Protected "8dqj" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:46, 27 July 2022

OCA: New page: '''Unreleased structure''' The entry 8dqj is ON HOLD Authors: Gottfried-Lee, I., Karplus, P.A., Mehl, R.A., Cooley, R.B. Description: Crystal structure of pyrrolysyl-tRNA synthetase fr...

OCA — Wed, 27 Jul 2022 16:46:40 GMT

New page: '''Unreleased structure''' The entry 8dqj is ON HOLD Authors: Gottfried-Lee, I., Karplus, P.A., Mehl, R.A., Cooley, R.B. Description: Crystal structure of pyrrolysyl-tRNA synthetase fr...

New page

'''Unreleased structure'''

The entry 8dqj is ON HOLD

Authors: Gottfried-Lee, I., Karplus, P.A., Mehl, R.A., Cooley, R.B.

Description: Crystal structure of pyrrolysyl-tRNA synthetase from Methanomethylophilus alvus engineered for acridone amino acid (AST) bound to ATP and acridone
[[Category: Unreleased Structures]]
[[Category: Mehl, R.A]]
[[Category: Karplus, P.A]]
[[Category: Gottfried-Lee, I]]
[[Category: Cooley, R.B]]