OCA at 19:54, 19 September 2018

OCA — Wed, 19 Sep 2018 19:54:49 GMT

←Older revision		Revision as of 19:54, 19 September 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6exi is ~~ON HOLD until Paper~~ Publication	+	==NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhizobium elkanii complexed with adenosine==
		+	<StructureSection load='6exi' size='340' side='right' caption='[[6exi]], [[Resolution\|resolution]] 1.92Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6exi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EXI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4lvc\|4lvc]], [[5m5k\|5m5k]], [[5m55\|5m55]], [[5m56\|5m56]], [[5m57\|5m57]], [[5tow\|5tow]], [[5tov\|5tov]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteinase Adenosylhomocysteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.1.1 3.3.1.1] </span></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=6exi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6exi OCA], [http://pdbe.org/6exi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6exi RCSB], [http://www.ebi.ac.uk/pdbsum/6exi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6exi ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	S-adenosyl-L-homocysteine (SAH) hydrolases (SAHases) are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD(+)) as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB) are a promising tool to modulate SAHase activity. In the present in vitro study, we investigated 10 synthetic truncated NAD(+) analogs against a SAHase from the root-nodulating bacterium Bradyrhizobium elkanii. Among this set of analogs, one was identified to inhibit the SAHase in both directions. Isothermal titration calorimetry (ITC) and crystallography experiments suggest that the inhibitory effect is not mediated by a direct interaction with the protein. Neither the apo-enzyme (i.e., deprived of the natural cofactor), nor the holo-enzyme (i.e., in the NAD(+)-bound state) were found to bind the inhibitor. Yet, enzyme kinetics point to a non-competitive inhibition mechanism, where the inhibitor acts on both, the enzyme and enzyme-SAH complex. Based on our experimental results, we hypothesize that the NCB inhibits the enzyme via oxidation of the enzyme-bound NADH, which may be accessible through an open molecular gate, leaving the enzyme stalled in a configuration with oxidized cofactor, where the reaction intermediate can be neither converted nor released. Since the reaction mechanism of SAHase is quite uncommon, this kind of inhibition could be a viable pharmacological route, with a low risk of off-target effects. The NCB presented in this work could be used as a template for the development of more potent SAHase inhibitors.

-	~~Authors: Manszewski~~, T., Jaskolski, M.	+	S-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic.,Kailing LL, Bertinetti D, Paul CE, Manszewski T, Jaskolski M, Herberg FW, Pavlidis IV Front Microbiol. 2018 Mar 21;9:505. doi: 10.3389/fmicb.2018.00505. eCollection, 2018. PMID:29619018<ref>PMID:29619018</ref>

-	~~Description: NAD-free crystal structure~~ of S-~~adenosyl~~-~~L-homocysteine hydrolase from Bradyrhizobium elkanii complexed with adenosine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Manszewski, T~~]]	+	<div class="pdbe-citations 6exi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Adenosylhomocysteinase]]
	[[Category: Jaskolski, M]]		[[Category: Jaskolski, M]]
		+	[[Category: Manszewski, T]]
		+	[[Category: Adnosine]]
		+	[[Category: Hydorolase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Methylation]]
		+	[[Category: Methyltransferase]]
		+	[[Category: Nad]]
		+	[[Category: S-adenosyl-l-homocysteine]]
		+	[[Category: S-adenosyl-l-methionine]]
		+	[[Category: Sah]]
		+	[[Category: Sahase]]
		+	[[Category: Sam]]

OCA at 06:10, 6 December 2017

OCA — Wed, 06 Dec 2017 06:10:10 GMT

←Older revision		Revision as of 06:10, 6 December 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6exi is ON HOLD	+	The entry 6exi is ON HOLD until Paper Publication

	Authors: Manszewski, T., Jaskolski, M.		Authors: Manszewski, T., Jaskolski, M.

OCA at 06:40, 22 November 2017

OCA — Wed, 22 Nov 2017 06:40:35 GMT

←Older revision		Revision as of 06:40, 22 November 2017
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	Authors: Manszewski, T., Jaskolski, M.		Authors: Manszewski, T., Jaskolski, M.

-	Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhizobium ~~Elkanii~~ complexed with adenosine	+	Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhizobium elkanii complexed with adenosine
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Manszewski, T]]		[[Category: Manszewski, T]]
	[[Category: Jaskolski, M]]		[[Category: Jaskolski, M]]

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

OCA — Wed, 15 Nov 2017 06:31:48 GMT

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

←Older revision

Revision as of 06:31, 15 November 2017

OCA: New page: '''Unreleased structure''' The entry 6exi is ON HOLD Authors: Manszewski, T., Jaskolski, M. Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhi...

OCA — Wed, 15 Nov 2017 06:31:46 GMT

New page: '''Unreleased structure''' The entry 6exi is ON HOLD Authors: Manszewski, T., Jaskolski, M. Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhi...

New page

'''Unreleased structure'''

The entry 6exi is ON HOLD

Authors: Manszewski, T., Jaskolski, M.

Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhizobium Elkanii complexed with adenosine
[[Category: Unreleased Structures]]
[[Category: Manszewski, T]]
[[Category: Jaskolski, M]]

6exi - Revision history

OCA at 19:54, 19 September 2018

OCA at 06:10, 6 December 2017

OCA at 06:40, 22 November 2017

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

OCA: New page: '''Unreleased structure''' The entry 6exi is ON HOLD Authors: Manszewski, T., Jaskolski, M. Description: NAD-free crystal structure of S-adenosyl-L-homocysteine hydrolase from Bradyrhi...