5oa4 - Revision history

OCA at 09:38, 6 December 2023

2023-12-06T09:38:10Z

←Older revision		Revision as of 09:38, 6 December 2023
Line 3:		Line 3:
	<StructureSection load='5oa4' size='340' side='right'caption='[[5oa4]], [[Resolution\|resolution]] 1.55Å' scene=''>		<StructureSection load='5oa4' size='340' side='right'caption='[[5oa4]], [[Resolution\|resolution]] 1.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5oa4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5OA4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5oa4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans_FGSC_A4 Aspergillus nidulans FGSC A4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OA4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=58D:(3S)-3-(4-METHOXYBENZYL)-4-METHYL-3,4-DIHYDRO-1H-1,4-BENZODIAZEPINE-2,5-DIONE'>58D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.55Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dap\|5dap]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=58D:(3S)-3-(4-METHOXYBENZYL)-4-METHYL-3,4-DIHYDRO-1H-1,4-BENZODIAZEPINE-2,5-DIONE'>58D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=5oa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa4 OCA], [~~http~~://pdbe.org/5oa4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5oa4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5oa4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa4 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=5oa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa4 OCA], [https://pdbe.org/5oa4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oa4 RCSB], [https://www.ebi.ac.uk/pdbsum/5oa4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ASQJ_EMENI ASQJ_EMENI]] Iron/alpha-ketoglutarate-dependent dioxygenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:26553478). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin proceeds non-enzymatically (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin and cyclopenin in a sequential fashion (PubMed:25251934). Cyclopenin can be converted into viridicatin non-enzymatically (PubMed:25251934). 4'-methoxyviridicatin likely acts as a precursor of quinolone natural products, such as aspoquinolones, peniprequinolones, penigequinolones, and yaequinolones (PubMed:25251934). Further characterization of the remaining genes in the cluster has still to be done to determine the exact identity of quinolone products this cluster is responsible for biosynthesizing (PubMed:25251934).<ref>PMID:25251934</ref> <ref>PMID:26553478</ref>	+	[https://www.uniprot.org/uniprot/ASQJ_EMENI ASQJ_EMENI] Iron/alpha-ketoglutarate-dependent dioxygenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:26553478). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin proceeds non-enzymatically (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin and cyclopenin in a sequential fashion (PubMed:25251934). Cyclopenin can be converted into viridicatin non-enzymatically (PubMed:25251934). 4'-methoxyviridicatin likely acts as a precursor of quinolone natural products, such as aspoquinolones, peniprequinolones, penigequinolones, and yaequinolones (PubMed:25251934). Further characterization of the remaining genes in the cluster has still to be done to determine the exact identity of quinolone products this cluster is responsible for biosynthesizing (PubMed:25251934).<ref>PMID:25251934</ref> <ref>PMID:26553478</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Aspergillus nidulans FGSC A4]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Braeuer, A]]	+	[[Category: Braeuer A]]
-	[[Category: Groll, M]]	+	[[Category: Groll M]]
-	[[Category: Kaila~~, V R.I]]~~	+	[[Category: Kaila VRI]]
-	~~[[Category: Antibiotic]]~~	+
-	~~[[Category: Catalytic mechanism]]~~	+
-	~~[[Category: Desaturase]]~~	+
-	~~[[Category: Molecular engineering]]~~	+
-	~~[[Category: Mutagenesis]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Pi-stacking]]~~	+
-	~~[[Category: Quinolone biosynthesis~~]]	+

OCA at 12:19, 26 August 2020

2020-08-26T12:19:43Z

←Older revision		Revision as of 12:19, 26 August 2020
Line 1:		Line 1:

	==Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in complex with 4-methoxycyclopeptin (1)==		==Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in complex with 4-methoxycyclopeptin (1)==
-	<StructureSection load='5oa4' size='340' side='right' caption='[[5oa4]], [[Resolution\|resolution]] 1.55Å' scene=''>	+	<StructureSection load='5oa4' size='340' side='right'caption='[[5oa4]], [[Resolution\|resolution]] 1.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5oa4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA4 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OA4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5oa4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OA4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=58D:(3S)-3-(4-METHOXYBENZYL)-4-METHYL-3,4-DIHYDRO-1H-1,4-BENZODIAZEPINE-2,5-DIONE'>58D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=58D:(3S)-3-(4-METHOXYBENZYL)-4-METHYL-3,4-DIHYDRO-1H-1,4-BENZODIAZEPINE-2,5-DIONE'>58D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dap\|5dap]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dap\|5dap]]</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=5oa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa4 OCA], [http://pdbe.org/5oa4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oa4 RCSB], [http://www.ebi.ac.uk/pdbsum/5oa4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa4 ProSAT]</span></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=5oa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa4 OCA], [http://pdbe.org/5oa4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oa4 RCSB], [http://www.ebi.ac.uk/pdbsum/5oa4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa4 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5oa4" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5oa4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dioxygenase 3D structures\|Dioxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Braeuer, A]]		[[Category: Braeuer, A]]
	[[Category: Groll, M]]		[[Category: Groll, M]]

OCA at 05:52, 4 April 2018

2018-04-04T05:52:14Z

←Older revision		Revision as of 05:52, 4 April 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5oa4 is ~~ON HOLD~~	+	==Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in complex with 4-methoxycyclopeptin (1)==
		+	<StructureSection load='5oa4' size='340' side='right' caption='[[5oa4]], [[Resolution\|resolution]] 1.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5oa4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OA4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OA4 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=58D:(3S)-3-(4-METHOXYBENZYL)-4-METHYL-3,4-DIHYDRO-1H-1,4-BENZODIAZEPINE-2,5-DIONE'>58D</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5dap\|5dap]]</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=5oa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oa4 OCA], [http://pdbe.org/5oa4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oa4 RCSB], [http://www.ebi.ac.uk/pdbsum/5oa4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oa4 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ASQJ_EMENI ASQJ_EMENI]] Iron/alpha-ketoglutarate-dependent dioxygenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:26553478). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin proceeds non-enzymatically (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin and cyclopenin in a sequential fashion (PubMed:25251934). Cyclopenin can be converted into viridicatin non-enzymatically (PubMed:25251934). 4'-methoxyviridicatin likely acts as a precursor of quinolone natural products, such as aspoquinolones, peniprequinolones, penigequinolones, and yaequinolones (PubMed:25251934). Further characterization of the remaining genes in the cluster has still to be done to determine the exact identity of quinolone products this cluster is responsible for biosynthesizing (PubMed:25251934).<ref>PMID:25251934</ref> <ref>PMID:26553478</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The recently discovered Fe(II)/alpha-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans stereoselectively catalyzes a multistep synthesis of quinolone alkaloids, natural products with significant biomedical applications. To probe molecular mechanisms of this elusive catalytic process, we combine here multi-scale quantum and classical molecular simulations with X-ray crystallography, and in vitro biochemical activity studies. We discover that methylation of the substrate is essential for the activity of AsqJ, establishing molecular strain that fine-tunes pi-stacking interactions within the active site. To rationally engineer AsqJ for modified substrates, we amplify dispersive interactions within the active site. We demonstrate that the engineered enzyme has a drastically enhanced catalytic activity for non-methylated surrogates, confirming our computational data and resolved high-resolution X-ray structures at 1.55 A resolution. Our combined findings provide crucial mechanistic understanding of the function of AsqJ and showcase how combination of computational and experimental data enables to rationally engineer enzymes.

-	~~Authors: Groll, M~~., ~~Braeuer~~, A., ~~Kaila~~, V.R.I.	+	Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ.,Mader SL, Brauer A, Groll M, Kaila VRI Nat Commun. 2018 Mar 21;9(1):1168. doi: 10.1038/s41467-018-03442-2. PMID:29563492<ref>PMID:29563492</ref>

-	~~Description: Fe(II)~~/~~(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in complex with 4-methoxycyclopeptin (1)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category: Kaila~~, V.R.~~I]]~~	+	<div class="pdbe-citations 5oa4" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Groll, M]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Braeuer, A]]		[[Category: Braeuer, A]]
		+	[[Category: Groll, M]]
		+	[[Category: Kaila, V R.I]]
		+	[[Category: Antibiotic]]
		+	[[Category: Catalytic mechanism]]
		+	[[Category: Desaturase]]
		+	[[Category: Molecular engineering]]
		+	[[Category: Mutagenesis]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Pi-stacking]]
		+	[[Category: Quinolone biosynthesis]]

OCA: Protected "5oa4" [edit=sysop:move=sysop]

2017-09-27T12:12:11Z

Protected "5oa4" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:12, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5oa4 is ON HOLD Authors: Groll, M., Braeuer, A., Kaila, V.R.I. Description: Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in c...

2017-09-27T12:12:10Z

New page: '''Unreleased structure''' The entry 5oa4 is ON HOLD Authors: Groll, M., Braeuer, A., Kaila, V.R.I. Description: Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in c...

New page

'''Unreleased structure'''

The entry 5oa4 is ON HOLD

Authors: Groll, M., Braeuer, A., Kaila, V.R.I.

Description: Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AsqJ_V72I mutant in complex with 4-methoxycyclopeptin (1)
[[Category: Unreleased Structures]]
[[Category: Kaila, V.R.I]]
[[Category: Groll, M]]
[[Category: Braeuer, A]]