8coy - Revision history

OCA at 06:12, 19 July 2023

OCA — Wed, 19 Jul 2023 06:12:03 GMT

←Older revision		Revision as of 06:12, 19 July 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8coy is ~~ON HOLD until Paper~~ Publication	+	==Structure of the catalytic domain of P. vivax Sub1 (triclinic crystal form) in complex with inhibitor==
		+	<StructureSection load='8coy' size='340' side='right'caption='[[8coy]], [[Resolution\|resolution]] 1.51Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8coy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8COY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8COY 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]] 1.507Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VEF:(3S)-3-azanyl-2,2-bis(oxidanyl)butanoic+acid'>VEF</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=8coy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8coy OCA], [https://pdbe.org/8coy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8coy RCSB], [https://www.ebi.ac.uk/pdbsum/8coy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8coy ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A564ZWC2_PLAVI A0A564ZWC2_PLAVI]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The constant selection and propagation of multi-resistant Plasmodium sp. parasites require the identification of new antimalarial candidates involved in as-yet untargeted metabolic pathways. Subtilisin-like protease 1 (SUB1) belongs to a new generation of drug targets because it plays a crucial role during egress of the parasite from infected host cells at different stages of its life cycle. SUB1 is characterized by an unusual pro-region that tightly interacts with its cognate catalytic domain, thus precluding 3D structural analysis of enzyme-inhibitor complexes. In the present study, to overcome this limitation, stringent ionic conditions and controlled proteolysis of recombinant full-length P. vivax SUB1 were used to obtain crystals of an active and stable catalytic domain (PvS1(Cat)) without a pro-region. High-resolution 3D structures of PvS1(Cat), alone and in complex with an alpha-ketoamide substrate-derived inhibitor (MAM-117), showed that, as expected, the catalytic serine of SUB1 formed a covalent bond with the alpha-keto group of the inhibitor. A network of hydrogen bonds and hydrophobic interactions stabilized the complex, including at the P1' and P2' positions of the inhibitor, although P' residues are usually less important in defining the substrate specificity of subtilisins. Moreover, when associated with a substrate-derived peptidomimetic inhibitor, the catalytic groove of SUB1 underwent significant structural changes, particularly in its S4 pocket. These findings pave the way for future strategies for the design of optimized SUB1-specific inhibitors that may define a novel class of antimalarial candidates.

-	~~Authors:~~ Martinez, M., Bouillon, A., ~~Batista~~, F., Alzari~~, P.M.~~, Barale~~, J~~.C.~~, Haouz, A~~.	+	3D structures of the Plasmodium vivax subtilisin-like drug target SUB1 reveal conformational changes to accommodate a substrate-derived alpha-ketoamide inhibitor.,Martinez M, Batista FA, Maurel M, Bouillon A, Ortega Varga L, Wehenkel AM, Le Chevalier-Sontag L, Blondel A, Haouz A, Hernandez JF, Alzari PM, Barale JC Acta Crystallogr D Struct Biol. 2023 Aug 1. doi: 10.1107/S2059798323004710. PMID:37428845<ref>PMID:37428845</ref>

-	~~Description: Structure~~ of the ~~catalytic domain~~ of P. ~~vivax Sub1 (triclinic crystal form) in complex with inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Martinez, M~~]]	+	<div class="pdbe-citations 8coy" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Batista, F~~]]	+	== References ==
-	[[Category: ~~Bouillon, A~~]]	+	<references/>
-	[[Category: Barale~~, J.C~~]]	+	__TOC__
-	[[Category: ~~Alzari, P.M~~]]	+	</StructureSection>
-	[[Category: Haouz, A]]	+	[[Category: Large Structures]]
		+	[[Category: Plasmodium vivax]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Alzari PM]]
		+	[[Category: Barale JC]]
		+	[[Category: Batista F]]
		+	[[Category: Bouillon A]]
		+	[[Category: Haouz A]]
		+	[[Category: Martinez M]]

OCA at 03:50, 5 July 2023

OCA — Wed, 05 Jul 2023 03:50:58 GMT

←Older revision		Revision as of 03:50, 5 July 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.		Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.

OCA at 04:10, 7 June 2023

OCA — Wed, 07 Jun 2023 04:10:03 GMT

←Older revision		Revision as of 04:10, 7 June 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8coy is ON HOLD ~~until Paper Publication~~	+	The entry 8coy is ON HOLD

	Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.		Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.
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	Description: Structure of the catalytic domain of P. vivax Sub1 (triclinic crystal form) in complex with inhibitor		Description: Structure of the catalytic domain of P. vivax Sub1 (triclinic crystal form) in complex with inhibitor
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Bouillon, A]]
	[[Category: Martinez, M]]		[[Category: Martinez, M]]
	[[Category: Batista, F]]		[[Category: Batista, F]]
		+	[[Category: Bouillon, A]]
	[[Category: Barale, J.C]]		[[Category: Barale, J.C]]
	[[Category: Alzari, P.M]]		[[Category: Alzari, P.M]]
	[[Category: Haouz, A]]		[[Category: Haouz, A]]

OCA at 05:36, 22 March 2023

OCA — Wed, 22 Mar 2023 05:36:38 GMT

←Older revision		Revision as of 05:36, 22 March 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.		Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.

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

OCA — Wed, 08 Mar 2023 05:40:14 GMT

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

←Older revision

Revision as of 05:40, 8 March 2023

OCA: New page: '''Unreleased structure''' The entry 8coy is ON HOLD Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A. Description: Structure of the catalytic dom...

OCA — Wed, 08 Mar 2023 05:40:13 GMT

New page: '''Unreleased structure''' The entry 8coy is ON HOLD Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A. Description: Structure of the catalytic dom...

New page

'''Unreleased structure'''

The entry 8coy is ON HOLD

Authors: Martinez, M., Bouillon, A., Batista, F., Alzari, P.M., Barale, J.C., Haouz, A.

Description: Structure of the catalytic domain of P. vivax Sub1 (triclinic crystal form) in complex with inhibitor
[[Category: Unreleased Structures]]
[[Category: Bouillon, A]]
[[Category: Martinez, M]]
[[Category: Batista, F]]
[[Category: Barale, J.C]]
[[Category: Alzari, P.M]]
[[Category: Haouz, A]]