7my9 - Revision history

OCA at 16:21, 18 October 2023

OCA — Wed, 18 Oct 2023 16:21:21 GMT

←Older revision		Revision as of 16:21, 18 October 2023
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	<StructureSection load='7my9' size='340' side='right'caption='[[7my9]], [[Resolution\|resolution]] 1.63Å' scene=''>		<StructureSection load='7my9' size='340' side='right'caption='[[7my9]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7my9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7my9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sinorhizobium_meliloti_SM11 Sinorhizobium meliloti SM11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UJD:1,3-dithiolane-2-carboxylic+acid'>UJD</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]] 1.628Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UJD:1,3-dithiolane-2-carboxylic+acid'>UJD</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=7my9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my9 OCA], [https://pdbe.org/7my9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my9 RCSB], [https://www.ebi.ac.uk/pdbsum/7my9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my9 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=7my9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my9 OCA], [https://pdbe.org/7my9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my9 RCSB], [https://www.ebi.ac.uk/pdbsum/7my9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/F7X6I3_SINMM F7X6I3_SINMM]] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197]	+	[https://www.uniprot.org/uniprot/F7X6I3_SINMM F7X6I3_SINMM] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7my9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7my9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Proline utilization A\|Proline utilization A]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Campbell, A C~~]]	+	[[Category: Sinorhizobium meliloti SM11]]
-	[[Category: ~~Tanner, J J~~]]	+	[[Category: Campbell AC]]
-	[[Category: ~~Aldehyde dehydrogenase]]~~	+	[[Category: Tanner JJ]]
-	~~[[Category: Bifunctional enzyme]]~~	+
-	~~[[Category: Flavoenzyme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Proline catabolism]]~~	+
-	~~[[Category: Proline dehydrognease]]~~	+
-	~~[[Category: Rossmann fold]]~~	+
-	~~[[Category: Substrate channeling~~]]	+

OCA at 06:28, 1 December 2021

OCA — Wed, 01 Dec 2021 06:28:59 GMT

←Older revision		Revision as of 06:28, 1 December 2021
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	==Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site==		==Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site==
-	<StructureSection load='7my9' size='340' side='right'caption='[[7my9]]' scene=''>	+	<StructureSection load='7my9' size='340' side='right'caption='[[7my9]], [[Resolution\|resolution]] 1.63Å' 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=7MY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7my9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY9 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=7my9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my9 OCA], [https://pdbe.org/7my9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my9 RCSB], [https://www.ebi.ac.uk/pdbsum/7my9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my9 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=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UJD:1,3-dithiolane-2-carboxylic+acid'>UJD</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=7my9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my9 OCA], [https://pdbe.org/7my9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my9 RCSB], [https://www.ebi.ac.uk/pdbsum/7my9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my9 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/F7X6I3_SINMM F7X6I3_SINMM]] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proline dehydrogenase (PRODH) is a flavoenzyme that catalyzes the first step of proline catabolism, the oxidation of l-proline to Delta(1)-pyrroline-5-carboxylate. PRODH has emerged as a cancer therapy target because of its involvement in the metabolic reprogramming of cancer cells. Here, we report the discovery of a new class of PRODH inactivator, which covalently and irreversibly modifies the FAD in a light-dependent manner. Two examples, 1,3-dithiolane-2-carboxylate and tetrahydrothiophene-2-carboxylate, have been characterized using X-ray crystallography (1.52-1.85 A resolution), absorbance spectroscopy, and enzyme kinetics. The structures reveal that in the dark, these compounds function as classical reversible, proline analogue inhibitors. However, exposure of enzyme-inhibitor cocrystals to bright white light induces decarboxylation of the inhibitor and covalent attachment of the residual S-heterocycle to the FAD N5 atom, locking the cofactor into a reduced, inactive state. Spectroscopic measurements of the inactivation process in solution confirm the requirement for light and show that blue light is preferred. Enzyme activity assays show that the rate of inactivation is enhanced by light and that the inactivation is irreversible. We also demonstrate the photosensitivity of cancer cells to one of these compounds. A possible mechanism is proposed involving photoexcitation of the FAD, while the inhibitor is noncovalently bound in the active site, followed by electron transfer, decarboxylation, and radical combination steps. Our results could lead to the development of photopharmacological drugs targeting PRODH.
		+
		+	Photoinduced Covalent Irreversible Inactivation of Proline Dehydrogenase by S-Heterocycles.,Campbell AC, Prater AR, Bogner AN, Quinn TP, Gates KS, Becker DF, Tanner JJ ACS Chem Biol. 2021 Sep 20. doi: 10.1021/acschembio.1c00427. PMID:34542291<ref>PMID:34542291</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7my9" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Campbell AC]]	+	[[Category: Campbell, A C]]
-	[[Category: Tanner JJ]]	+	[[Category: Tanner, J J]]
		+	[[Category: Aldehyde dehydrogenase]]
		+	[[Category: Bifunctional enzyme]]
		+	[[Category: Flavoenzyme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Proline catabolism]]
		+	[[Category: Proline dehydrognease]]
		+	[[Category: Rossmann fold]]
		+	[[Category: Substrate channeling]]

OCA at 08:50, 29 September 2021

OCA — Wed, 29 Sep 2021 08:50:47 GMT

←Older revision		Revision as of 08:50, 29 September 2021
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-	'''Unreleased structure'''

-	~~The entry 7my9 is ON HOLD until Paper Publication~~	+	==Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site==
-		+	<StructureSection load='7my9' size='340' side='right'caption='[[7my9]]' scene=''>
-	~~Authors: Tanner, J.J., Campbell, A.C.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY9 FirstGlance]. <br>
-	~~Description:~~ Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site	+	</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=7my9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my9 OCA], [https://pdbe.org/7my9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my9 RCSB], [https://www.ebi.ac.uk/pdbsum/7my9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my9 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Tanner~~, J.J]]	+	__TOC__
-	[[Category: Campbell~~, A.C~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Campbell AC]]
		+	[[Category: Tanner JJ]]

OCA at 13:29, 2 June 2021

OCA — Wed, 02 Jun 2021 13:29:14 GMT

←Older revision		Revision as of 13:29, 2 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7my9 is ON HOLD	+	The entry 7my9 is ON HOLD until Paper Publication

	Authors: Tanner, J.J., Campbell, A.C.		Authors: Tanner, J.J., Campbell, A.C.
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	Description: Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site		Description: Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Campbell, A.C]]
	[[Category: Tanner, J.J]]		[[Category: Tanner, J.J]]
		+	[[Category: Campbell, A.C]]

OCA: Protected "7my9" [edit=sysop:move=sysop]

OCA — Wed, 26 May 2021 08:03:27 GMT

Protected "7my9" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:03, 26 May 2021

OCA: New page: '''Unreleased structure''' The entry 7my9 is ON HOLD Authors: Tanner, J.J., Campbell, A.C. Description: Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in th...

OCA — Wed, 26 May 2021 08:03:26 GMT

New page: '''Unreleased structure''' The entry 7my9 is ON HOLD Authors: Tanner, J.J., Campbell, A.C. Description: Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in th...

New page

'''Unreleased structure'''

The entry 7my9 is ON HOLD

Authors: Tanner, J.J., Campbell, A.C.

Description: Structure of proline utilization A with 1,3-dithiolane-2-carboxylate bound in the proline dehydrogenase active site
[[Category: Unreleased Structures]]
[[Category: Campbell, A.C]]
[[Category: Tanner, J.J]]