4zj6 - Revision history

OCA: Redirecting to 5f8x

OCA — Thu, 15 Dec 2016 18:56:48 GMT

Redirecting to 5f8x

←Older revision		Revision as of 18:56, 15 December 2016
Line 1:		Line 1:
-	~~==The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-3==~~	+	#REDIRECT [[5f8x]] This PDB entry is obsolete and replaced by 5f8x
-	~~<StructureSection load='4zj6' size='340' side='right' caption='~~[[~~4zj6~~]]~~, [[Resolution\|resolution]] 1.55Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	<table><tr><td colspan='2'>[[4zj6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJ6 FirstGlance]. <br>	+
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MRZ:PIPERIDINE-1-CARBOXIMIDAMIDE'>MRZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zj4\|4zj4]], [[4zj5\|4zj5]]</td></tr>~~	+
-	<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>	+
-	<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=4zj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zj6 OCA], [http://pdbe.org/4zj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zj6 PDBsum]</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.~~	+
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	All serine proteases hydrolyze peptide bonds by the same basic mechanism and have very similar active sites, in spite of the fact that individual proteases have different physiological functions. We here report a strategy for designing high-affinity and high-specificity serine protease inhibitors using a versatile peptide scaffold, a 10-mer peptide, mupain-1 (CPAYSRYLDC). Mupain-1 was previously reported as a specific inhibitor of murine urokinase-type plasminogen activator (Ki = 0.55 muM) without measurable affinity to plasma kallikrein (Ki > 1000 muM). On the basis of a structure-based rational design, we substituted five residues of mupain-1 and converted it to a potent plasma kallikrein inhibitor (Ki = 0.014 muM). X-ray crystal structure analysis showed that the new peptide was able to adapt a new set of enzyme surface interactions by a slightly changed backbone conformation. Thus, with an appropriate re-engineering, mupain-1 can be redesigned to specific inhibitors of other serine proteases.	+
-		+
-	Design of Specific Serine Protease Inhibitors Based on a Versatile Peptide Scaffold: Conversion of a Urokinase Inhibitor to a Plasma Kallikrein Inhibitor.,Xu P, Xu M, Jiang L, Yang Q, Luo Z, Dauter Z, Huang M, Andreasen PA J Med Chem. 2015 Nov 25;58(22):8868-76. doi: 10.1021/acs.jmedchem.5b01128. Epub, 2015 Nov 12. PMID:26536069<ref>PMID:26536069</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4zj6" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Plasma kallikrein]]~~	+
-	~~[[Category: Andreasen, P]]~~	+
-	~~[[Category: Huang, M]]~~	+
-	~~[[Category: Jiang, L]]~~	+
-	~~[[Category: Luo, Z]]~~	+
-	~~[[Category: Xu, M]]~~	+
-	~~[[Category: Xu, P]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Peptide inhibitor]]~~	+

OCA at 18:57, 1 December 2015

OCA — Tue, 01 Dec 2015 18:57:55 GMT

←Older revision		Revision as of 18:57, 1 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-3==
		+	<StructureSection load='4zj6' size='340' side='right' caption='[[4zj6]], [[Resolution\|resolution]] 1.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zj6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZJ6 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MRZ:PIPERIDINE-1-CARBOXIMIDAMIDE'>MRZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zj4\|4zj4]], [[4zj5\|4zj5]]</td></tr>
		+	<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>
		+	<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=4zj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zj6 OCA], [http://pdbe.org/4zj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4zj6 PDBsum]</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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	All serine proteases hydrolyze peptide bonds by the same basic mechanism and have very similar active sites, in spite of the fact that individual proteases have different physiological functions. We here report a strategy for designing high-affinity and high-specificity serine protease inhibitors using a versatile peptide scaffold, a 10-mer peptide, mupain-1 (CPAYSRYLDC). Mupain-1 was previously reported as a specific inhibitor of murine urokinase-type plasminogen activator (Ki = 0.55 muM) without measurable affinity to plasma kallikrein (Ki > 1000 muM). On the basis of a structure-based rational design, we substituted five residues of mupain-1 and converted it to a potent plasma kallikrein inhibitor (Ki = 0.014 muM). X-ray crystal structure analysis showed that the new peptide was able to adapt a new set of enzyme surface interactions by a slightly changed backbone conformation. Thus, with an appropriate re-engineering, mupain-1 can be redesigned to specific inhibitors of other serine proteases.

-	~~The entry 4zj6 is ON HOLD until Paper Publication~~	+	Design of Specific Serine Protease Inhibitors Based on a Versatile Peptide Scaffold: Conversion of a Urokinase Inhibitor to a Plasma Kallikrein Inhibitor.,Xu P, Xu M, Jiang L, Yang Q, Luo Z, Dauter Z, Huang M, Andreasen PA J Med Chem. 2015 Nov 25;58(22):8868-76. doi: 10.1021/acs.jmedchem.5b01128. Epub, 2015 Nov 12. PMID:26536069<ref>PMID:26536069</ref>

-	~~Authors: Xu~~, M.~~, Jiang, L~~.~~, Xu, P., Luo, Z., Andreasen, P., Huang, M~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-3~~	+	<div class="pdbe-citations 4zj6" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Plasma kallikrein]]
	[[Category: Andreasen, P]]		[[Category: Andreasen, P]]
-	[[Category: Xu, P]]
-	[[Category: Xu, M]]
	[[Category: Huang, M]]		[[Category: Huang, M]]
	[[Category: Jiang, L]]		[[Category: Jiang, L]]
	[[Category: Luo, Z]]		[[Category: Luo, Z]]
		+	[[Category: Xu, M]]
		+	[[Category: Xu, P]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Peptide inhibitor]]

OCA at 12:02, 10 June 2015

OCA — Wed, 10 Jun 2015 12:02:14 GMT

←Older revision		Revision as of 12:02, 10 June 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zj6 is ON HOLD	+	The entry 4zj6 is ON HOLD until Paper Publication

	Authors: Xu, M., Jiang, L., Xu, P., Luo, Z., Andreasen, P., Huang, M.		Authors: Xu, M., Jiang, L., Xu, P., Luo, Z., Andreasen, P., Huang, M.

OCA at 10:48, 20 May 2015

OCA — Wed, 20 May 2015 10:48:42 GMT

←Older revision		Revision as of 10:48, 20 May 2015
Line 3:		Line 3:
	The entry 4zj6 is ON HOLD		The entry 4zj6 is ON HOLD

-	Authors: ~~Mingming~~ Xu, ~~Longguang~~ Jiang, ~~Peng~~ Xu, ~~Zhipu~~ Luo, ~~Peter~~ Andreasen, ~~Mingdong~~ Huang	+	Authors: Xu, M., Jiang, L., Xu, P., Luo, Z., Andreasen, P., Huang, M.

-	Description: The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-2	+	Description: The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-3
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Mingming~~ Xu, ~~Longguang Jiang, Peng~~ Xu, ~~Zhipu Luo~~, ~~Peter Andreasen~~, ~~Mingdong Huang~~]]	+	[[Category: Andreasen, P]]
		+	[[Category: Xu, P]]
		+	[[Category: Xu, M]]
		+	[[Category: Huang, M]]
		+	[[Category: Jiang, L]]
		+	[[Category: Luo, Z]]

OCA: Protected "4zj6" [edit=sysop:move=sysop]

OCA — Wed, 06 May 2015 11:48:55 GMT

Protected "4zj6" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:48, 6 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zj6 is ON HOLD Authors: Mingming Xu, Longguang Jiang, Peng Xu, Zhipu Luo, Peter Andreasen, Mingdong Huang Description: The crystal structure of hu...

OCA — Wed, 06 May 2015 11:48:53 GMT

New page: '''Unreleased structure''' The entry 4zj6 is ON HOLD Authors: Mingming Xu, Longguang Jiang, Peng Xu, Zhipu Luo, Peter Andreasen, Mingdong Huang Description: The crystal structure of hu...

New page

'''Unreleased structure'''

The entry 4zj6 is ON HOLD

Authors: Mingming Xu, Longguang Jiang, Peng Xu, Zhipu Luo, Peter Andreasen, Mingdong Huang

Description: The crystal structure of human Plasma Kallikrein in complex with its peptide inhibitor pkalin-2
[[Category: Unreleased Structures]]
[[Category: Mingming Xu, Longguang Jiang, Peng Xu, Zhipu Luo, Peter Andreasen, Mingdong Huang]]