6o1g - Revision history

OCA at 07:12, 27 March 2019

OCA — Wed, 27 Mar 2019 07:12:54 GMT

←Older revision		Revision as of 07:12, 27 March 2019
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	==Full length human plasma kallikrein with inhibitor==		==Full length human plasma kallikrein with inhibitor==
-	<StructureSection load='6o1g' size='340' side='right' caption='[[6o1g]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='6o1g' size='340' side='right'caption='[[6o1g]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6o1g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O1G FirstGlance]. <br>		<table><tr><td colspan='2'>[[6o1g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O1G FirstGlance]. <br>
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	== Function ==		== Function ==
	[[http://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.		[[http://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 ==
		+	Plasma kallikrein (pKal) is a serine protease responsible for cleaving high-molecular-weight kininogen to produce the pro-inflammatory peptide, bradykinin. Unregulated pKal activity can lead to hereditary angioedema (HAE) following excess bradykinin release. HAE attacks can lead to a compromised airway that can be life threatening. As there are limited agents for prophylaxis of HAE attacks, there is a high unmet need for a therapeutic agent for regulating pKal with a high degree of specificity. Here we present crystal structures of both full-length and the protease domain of pKal, bound to two very distinct classes of small-molecule inhibitors: compound 1, and BCX4161. Both inhibitors demonstrate low nM inhibitory potency for pKal and varying specificity for related serine proteases. Compound 1 utilizes a surprising mode of interaction and upon binding results in a rearrangement of the binding pocket. Co-crystal structures of pKal describes why this class of small-molecule inhibitor is potent. Lack of conservation in surrounding residues explains the approximately 10,000-fold specificity over structurally similar proteases, as shown by in vitro protease inhibition data. Structural information, combined with biochemical and enzymatic analyses, provides a novel scaffold for the design of targeted oral small molecule inhibitors of pKal for treatment of HAE and other diseases resulting from unregulated plasma kallikrein activity.
		+
		+	Structures of full-length plasma kallikrein bound to highly specific inhibitors describe a new mode of targeted inhibition.,Partridge JR, Choy RM, Silva-Garcia A, Yu C, Li Z, Sham H, Metcalf B J Struct Biol. 2019 Mar 12. pii: S1047-8477(19)30046-2. doi:, 10.1016/j.jsb.2019.03.001. PMID:30876891<ref>PMID:30876891</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6o1g" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Plasma kallikrein]]		[[Category: Plasma kallikrein]]
	[[Category: Choy, R M]]		[[Category: Choy, R M]]

OCA at 07:37, 6 March 2019

OCA — Wed, 06 Mar 2019 07:37:14 GMT

←Older revision		Revision as of 07:37, 6 March 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6o1g is ~~ON HOLD~~	+	==Full length human plasma kallikrein with inhibitor==
-		+	<StructureSection load='6o1g' size='340' side='right' caption='[[6o1g]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~Authors~~: ~~Partridge~~, J.R., ~~Choy~~, R.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6o1g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O1G FirstGlance]. <br>
-	~~Description~~: ~~Full length human plasma kallikrein with inhibitor~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SD:N-[(6-amino-2,4-dimethylpyridin-3-yl)methyl]-1-({4-[(1H-pyrazol-1-yl)methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide'>7SD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tz9\|5tz9]], [[6bfp\|6bfp]]</td></tr>
-	[[Category: Choy, R.M]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasma_kallikrein Plasma kallikrein], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.34 3.4.21.34] </span></td></tr>
-	[[Category: Partridge, J.R]]	+	<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=6o1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o1g OCA], [http://pdbe.org/6o1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o1g RCSB], [http://www.ebi.ac.uk/pdbsum/6o1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o1g ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KLKB1_HUMAN KLKB1_HUMAN]] Defects in KLKB1 are the cause of prekallikrein deficiency (PKK deficiency) [MIM:[http://omim.org/entry/612423 612423]]; also known as Fletcher factor deficiency. This disorder is a blood coagulation defect.
		+	== Function ==
		+	[[http://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.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Plasma kallikrein]]
		+	[[Category: Choy, R M]]
		+	[[Category: Partridge, J R]]
		+	[[Category: Blood clotting]]
		+	[[Category: Protease]]

OCA: Protected "6o1g" [edit=sysop:move=sysop]

OCA — Wed, 27 Feb 2019 13:50:05 GMT

Protected "6o1g" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:50, 27 February 2019

OCA: New page: '''Unreleased structure''' The entry 6o1g is ON HOLD Authors: Partridge, J.R., Choy, R.M. Description: Full length human plasma kallikrein with inhibitor [[Category: Unreleased Structu...

OCA — Wed, 27 Feb 2019 13:50:03 GMT

New page: '''Unreleased structure''' The entry 6o1g is ON HOLD Authors: Partridge, J.R., Choy, R.M. Description: Full length human plasma kallikrein with inhibitor [[Category: Unreleased Structu...

New page

'''Unreleased structure'''

The entry 6o1g is ON HOLD

Authors: Partridge, J.R., Choy, R.M.

Description: Full length human plasma kallikrein with inhibitor
[[Category: Unreleased Structures]]
[[Category: Choy, R.M]]
[[Category: Partridge, J.R]]