OCA at 05:56, 11 October 2023

OCA — Wed, 11 Oct 2023 05:56:57 GMT

←Older revision		Revision as of 05:56, 11 October 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8fge is ~~ON HOLD until Paper~~ Publication	+	==Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with 4-(difluoromethyl)-6-(5-(2-(dimethylamino)ethyl)-2,3-difluorophenethyl)pyridin-2-amine dihydrochloride==
		+	<StructureSection load='8fge' size='340' side='right'caption='[[8fge]], [[Resolution\|resolution]] 1.89Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8fge]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FGE FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.89Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=XVA:4-(difluoromethyl)-6-(2-{5-[2-(dimethylamino)ethyl]-2,3-difluorophenyl}ethyl)pyridin-2-amine'>XVA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8fge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fge OCA], [https://pdbe.org/8fge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fge RCSB], [https://www.ebi.ac.uk/pdbsum/8fge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fge ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A series of potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors (hnNOS), based on a difluorobenzene ring linked to a 2-aminopyridine scaffold with different functionalities at the 4-position, is reported. In our efforts to develop novel nNOS inhibitors for the treatment of neurodegenerative diseases, we discovered 17, which showed excellent potency toward both rat (K(i) 15 nM) and human nNOS (K(i) 19 nM), with 1075-fold selectivity over human eNOS and 115-fold selectivity over human iNOS. 17 also showed excellent permeability (P(e) = 13.7 x 10(-6) cm s(-1)), a low efflux ratio (ER 0.48), along with good metabolic stability in mouse and human liver microsomes, with half-lives of 29 and >60 min, respectively. X-ray cocrystal structures of inhibitors bound with three NOS enzymes, namely, rat nNOS, human nNOS, and human eNOS, revealed detailed structure-activity relationships for the observed potency, selectivity, and permeability properties of the inhibitors.

-	~~Authors: Li~~, H., Poulos, T.L.	+	Potent, Selective, and Membrane Permeable 2-Amino-4-Substituted Pyridine-Based Neuronal Nitric Oxide Synthase Inhibitors.,Vasu D, Do HT, Li H, Hardy CD, Awasthi A, Poulos TL, Silverman RB J Med Chem. 2023 Jul 27;66(14):9934-9953. doi: 10.1021/acs.jmedchem.3c00782. Epub , 2023 Jul 11. PMID:37433128<ref>PMID:37433128</ref>

-	~~Description: Structure~~ of ~~rat neuronal nitric oxide synthase R349A mutant heme domain in complex with 4-(difluoromethyl)~~-6-~~(5-(2-(dimethylamino)ethyl)-2,3-difluorophenethyl)pyridin-2-amine dihydrochloride~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Li, H]]	+	<div class="pdbe-citations 8fge" style="background-color:#fffaf0;"></div>
-	[[Category: Poulos~~, T.L~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Li H]]
		+	[[Category: Poulos TL]]

OCA at 05:52, 28 December 2022

OCA — Wed, 28 Dec 2022 05:52:39 GMT

←Older revision		Revision as of 05:52, 28 December 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Li, H., Poulos, T.L.		Authors: Li, H., Poulos, T.L.

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

OCA — Wed, 21 Dec 2022 06:43:04 GMT

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

←Older revision

Revision as of 06:43, 21 December 2022

OCA: New page: '''Unreleased structure''' The entry 8fge is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with...

OCA — Wed, 21 Dec 2022 06:43:03 GMT

New page: '''Unreleased structure''' The entry 8fge is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with...

New page

'''Unreleased structure'''

The entry 8fge is ON HOLD

Authors: Li, H., Poulos, T.L.

Description: Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with 4-(difluoromethyl)-6-(5-(2-(dimethylamino)ethyl)-2,3-difluorophenethyl)pyridin-2-amine dihydrochloride
[[Category: Unreleased Structures]]
[[Category: Li, H]]
[[Category: Poulos, T.L]]

8fge - Revision history

OCA at 05:56, 11 October 2023

OCA at 05:52, 28 December 2022

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

OCA: New page: '''Unreleased structure''' The entry 8fge is ON HOLD Authors: Li, H., Poulos, T.L. Description: Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with...