8a3q - Revision history

OCA at 13:36, 1 February 2024

OCA — Thu, 01 Feb 2024 13:36:25 GMT

←Older revision		Revision as of 13:36, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8a3q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A3Q FirstGlance]. <br>		<table><tr><td colspan='2'>[[8a3q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A3Q FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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]] 1.801Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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=8a3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a3q OCA], [https://pdbe.org/8a3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a3q RCSB], [https://www.ebi.ac.uk/pdbsum/8a3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a3q 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=8a3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a3q OCA], [https://pdbe.org/8a3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a3q RCSB], [https://www.ebi.ac.uk/pdbsum/8a3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a3q ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 8a3q" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 8a3q" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kallikrein 3D structures\|Kallikrein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:23, 3 November 2022

OCA — Thu, 03 Nov 2022 07:23:10 GMT

←Older revision		Revision as of 07:23, 3 November 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 8a3q is ~~ON HOLD until Paper~~ Publication	+	==Human Plasma Kallekrein in complex with 14W==
		+	<StructureSection load='8a3q' size='340' side='right'caption='[[8a3q]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8a3q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A3Q FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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=8a3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a3q OCA], [https://pdbe.org/8a3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a3q RCSB], [https://www.ebi.ac.uk/pdbsum/8a3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a3q ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/KLKB1_HUMAN KLKB1_HUMAN] Defects in KLKB1 are the cause of prekallikrein deficiency (PKK deficiency) [MIM:[https://omim.org/entry/612423 612423]; also known as Fletcher factor deficiency. This disorder is a blood coagulation defect.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KLKB1_HUMAN KLKB1_HUMAN] The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hereditary angioedema (HAE) is a rare genetic disorder in which patients experience sudden onset of swelling in various locations of the body. HAE is associated with uncontrolled plasma kallikrein (PKa) enzyme activity and generation of the potent inflammatory mediator, bradykinin, resulting in episodic attacks of angioedema. Herein, we disclose the discovery and optimization of novel small molecule PKa inhibitors. Starting from molecules containing highly basic P1 groups, which typically bind to an aspartic acid residue (Asp189) in the serine protease S1 pocket, we identified novel P1 binding groups likely to have greater potential for oral-drug-like properties. The optimization of P4 and the central core together with the particularly favorable properties of 3-fluoro-4-methoxypyridine P1 led to the development of sebetralstat, a potent, selective, orally bioavailable PKa inhibitor in phase 3 for on-demand treatment of HAE attacks.

-	~~Authors~~: McEwan, P.A.	+	Sebetralstat (KVD900): A Potent and Selective Small Molecule Plasma Kallikrein Inhibitor Featuring a Novel P1 Group as a Potential Oral On-Demand Treatment for Hereditary Angioedema.,Davie RL, Edwards HJ, Evans DM, Hodgson ST, Stocks MJ, Smith AJ, Rushbrooke LJ, Pethen SJ, Roe MB, Clark DE, McEwan PA, Hampton SL J Med Chem. 2022 Oct 27;65(20):13629-13644. doi: 10.1021/acs.jmedchem.2c00921., Epub 2022 Oct 17. PMID:36251573<ref>PMID:36251573</ref>

-	~~Description~~: ~~Human Plasma Kallekrein in complex with 14W~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Mcewan, P.A~~]]	+	<div class="pdbe-citations 8a3q" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: McEwan PA]]

OCA at 04:06, 13 July 2022

OCA — Wed, 13 Jul 2022 04:06:28 GMT

←Older revision		Revision as of 04:06, 13 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8a3q is ON HOLD	+	The entry 8a3q is ON HOLD until Paper Publication

	Authors: McEwan, P.A.		Authors: McEwan, P.A.

OCA: Protected "8a3q" [edit=sysop:move=sysop]

OCA — Wed, 15 Jun 2022 04:07:51 GMT

Protected "8a3q" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:07, 15 June 2022

OCA: New page: '''Unreleased structure''' The entry 8a3q is ON HOLD Authors: McEwan, P.A. Description: Human Plasma Kallekrein in complex with 14W Category: Unreleased Structures [[Category: Mcew...

OCA — Wed, 15 Jun 2022 04:07:50 GMT

New page: '''Unreleased structure''' The entry 8a3q is ON HOLD Authors: McEwan, P.A. Description: Human Plasma Kallekrein in complex with 14W Category: Unreleased Structures [[Category: Mcew...

New page

'''Unreleased structure'''

The entry 8a3q is ON HOLD

Authors: McEwan, P.A.

Description: Human Plasma Kallekrein in complex with 14W
[[Category: Unreleased Structures]]
[[Category: Mcewan, P.A]]