OCA at 07:15, 3 November 2022

2022-11-03T07:15:59Z

←Older revision		Revision as of 07:15, 3 November 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7uai is ~~ON HOLD until Paper~~ Publication	+	==Meprin alpha helix in complex with fetuin-B==
		+	<StructureSection load='7uai' size='340' side='right'caption='[[7uai]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7uai]] is a 6 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=7UAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UAI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7uai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uai OCA], [https://pdbe.org/7uai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uai RCSB], [https://www.ebi.ac.uk/pdbsum/7uai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uai ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MEP1A_HUMAN MEP1A_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The zinc-dependent metalloprotease meprin alpha is predominantly expressed in the brush border membrane of proximal tubules in the kidney and enterocytes in the small intestine and colon. In normal tissue homeostasis meprin alpha performs key roles in inflammation, immunity, and extracellular matrix remodelling. Dysregulated meprin alpha is associated with acute kidney injury, sepsis, urinary tract infection, metastatic colorectal carcinoma, and inflammatory bowel disease. Accordingly, meprin alpha is the target of drug discovery programs. In contrast to meprin beta, meprin alpha is secreted into the extracellular space, whereupon it oligomerises to form giant assemblies and is the largest extracellular protease identified to date (~6 MDa). Here, using cryo-electron microscopy, we determine the high-resolution structure of the zymogen and mature form of meprin alpha, as well as the structure of the active form in complex with a prototype small molecule inhibitor and human fetuin-B. Our data reveal that meprin alpha forms a giant, flexible, left-handed helical assembly of roughly 22 nm in diameter. We find that oligomerisation improves proteolytic and thermal stability but does not impact substrate specificity or enzymatic activity. Furthermore, structural comparison with meprin beta reveal unique features of the active site of meprin alpha, and helical assembly more broadly.

-	~~Authors:~~ Bayly-Jones, C., Lupton, C~~.J.~~, ~~Fritz~~, C., ~~Schlenzig~~, D., Whisstock~~, J~~.C.	+	Helical ultrastructure of the metalloprotease meprin alpha in complex with a small molecule inhibitor.,Bayly-Jones C, Lupton CJ, Fritz C, Venugopal H, Ramsbeck D, Wermann M, Jager C, de Marco A, Schilling S, Schlenzig D, Whisstock JC Nat Commun. 2022 Oct 19;13(1):6178. doi: 10.1038/s41467-022-33893-7. PMID:36261433<ref>PMID:36261433</ref>

-	~~Description: Meprin alpha helix in complex with fetuin~~-B	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Bayly-Jones, C]]	+	<div class="pdbe-citations 7uai" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Schlenzig, D~~]]	+	== References ==
-	[[Category: Lupton~~, C.J~~]]	+	<references/>
-	[[Category: ~~Whisstock, J.C~~]]	+	__TOC__
-	[[Category: ~~Fritz, C~~]]	+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bayly-Jones C]]
		+	[[Category: Fritz C]]
		+	[[Category: Lupton CJ]]
		+	[[Category: Schlenzig D]]
		+	[[Category: Whisstock JC]]

OCA at 08:33, 13 April 2022

2022-04-13T08:33:25Z

←Older revision		Revision as of 08:33, 13 April 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7uai is ON HOLD	+	The entry 7uai is ON HOLD until Paper Publication

	Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C.		Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C.

OCA: Protected "7uai" [edit=sysop:move=sysop]

2022-03-23T09:50:20Z

Protected "7uai" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:50, 23 March 2022

OCA: New page: '''Unreleased structure''' The entry 7uai is ON HOLD Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C. Description: Meprin alpha helix in complex with f...

2022-03-23T09:50:19Z

New page: '''Unreleased structure''' The entry 7uai is ON HOLD Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C. Description: Meprin alpha helix in complex with f...

New page

'''Unreleased structure'''

The entry 7uai is ON HOLD

Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C.

Description: Meprin alpha helix in complex with fetuin-B
[[Category: Unreleased Structures]]
[[Category: Bayly-Jones, C]]
[[Category: Schlenzig, D]]
[[Category: Lupton, C.J]]
[[Category: Whisstock, J.C]]
[[Category: Fritz, C]]

7uai - Revision history

OCA at 07:15, 3 November 2022

OCA at 08:33, 13 April 2022

OCA: Protected "7uai" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7uai is ON HOLD Authors: Bayly-Jones, C., Lupton, C.J., Fritz, C., Schlenzig, D., Whisstock, J.C. Description: Meprin alpha helix in complex with f...