7juj - Revision history

OCA at 15:11, 18 October 2023

OCA — Wed, 18 Oct 2023 15:11:38 GMT

←Older revision		Revision as of 15:11, 18 October 2023
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	<StructureSection load='7juj' size='340' side='right'caption='[[7juj]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='7juj' size='340' side='right'caption='[[7juj]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7juj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Trycr Trycr~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JUJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7juj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JUJ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GN9:gallinamide+A~~,~~+bound+form'>GN9</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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]] 2.2Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[https:/~~/~~en.wikipedia.org/wiki/Cruzipain Cruzipain]~~, ~~with EC number [https~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.51 3.4.22.51]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN9:gallinamide+A,+bound+form'>GN9</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=7juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7juj OCA], [https://pdbe.org/7juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7juj RCSB], [https://www.ebi.ac.uk/pdbsum/7juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7juj 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=7juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7juj OCA], [https://pdbe.org/7juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7juj RCSB], [https://www.ebi.ac.uk/pdbsum/7juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7juj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR]] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.	+	[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7juj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7juj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cruzain\|Cruzain]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Cruzipain]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Trycr~~]]	+	[[Category: Trypanosoma cruzi]]
-	[[Category: Alvarez~~, L H~~]]	+	[[Category: Alvarez LH]]
-	[[Category: Gerwick~~, W H~~]]	+	[[Category: Gerwick WH]]
-	[[Category: McKerrow~~, J H~~]]	+	[[Category: McKerrow JH]]
-	[[Category: Podust~~, L M~~]]	+	[[Category: Podust LM]]
-	[[Category: Sharma, V]]	+	[[Category: Sharma V]]
-	[[Category: Silva~~, E B]]~~	+	[[Category: Silva EB]]
-	~~[[Category: Cruzain]]~~	+
-	~~[[Category: Cysteine protease]]~~	+
-	~~[[Category: Gallinamide]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 07:27, 2 March 2022

OCA — Wed, 02 Mar 2022 07:27:35 GMT

←Older revision		Revision as of 07:27, 2 March 2022
Line 1:		Line 1:

	==Cruzain bound to Gallinamide inhibitor==		==Cruzain bound to Gallinamide inhibitor==
-	<StructureSection load='7juj' size='340' side='right'caption='[[7juj]]' scene=''>	+	<StructureSection load='7juj' size='340' side='right'caption='[[7juj]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JUJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7juj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JUJ FirstGlance]. <br>
-	</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=7juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7juj OCA], [https://pdbe.org/7juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7juj RCSB], [https://www.ebi.ac.uk/pdbsum/7juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7juj ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GN9:gallinamide+A,+bound+form'>GN9</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cruzipain Cruzipain], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.51 3.4.22.51] </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=7juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7juj OCA], [https://pdbe.org/7juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7juj RCSB], [https://www.ebi.ac.uk/pdbsum/7juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7juj ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR]] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group. The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Gallinamide A, a metabolite of the marine cyanobacterium Schizothrix sp., selectively inhibits cathepsin L-like cysteine proteases. We evaluated the potency of gallinamide A and 23 synthetic analogues against intracellular Trypanosoma cruzi amastigotes and the cysteine protease, cruzain. We determined the co-crystal structures of cruzain with gallinamide A and two synthetic analogues at approximately 2 A. SAR data revealed that the N-terminal end of gallinamide A is loosely bound and weakly contributes in drug-target interactions. At the C-terminus, the intramolecular pi-pi stacking interactions between the aromatic substituents at P1' and P1 restrict the bioactive conformation of the inhibitors, thus minimizing the entropic loss associated with target binding. Molecular dynamics simulations showed that in the absence of an aromatic group at P1, the substituent at P1' interacts with tryptophan-184. The P1-P1' interactions had no effect on anti-cruzain activity, whereas anti-T. cruzi potency increased by approximately fivefold, likely due to an increase in solubility/permeability of the analogues.
		+
		+	Intramolecular Interactions Enhance the Potency of Gallinamide A Analogues against Trypanosoma cruzi.,Barbosa Da Silva E, Sharma V, Hernandez-Alvarez L, Tang AH, Stoye A, O'Donoghue AJ, Gerwick WH, Payne RJ, McKerrow JH, Podust LM J Med Chem. 2022 Feb 21. doi: 10.1021/acs.jmedchem.1c02063. PMID:35188371<ref>PMID:35188371</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7juj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Cruzipain]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Alvarez LH]]	+	[[Category: Trycr]]
-	[[Category: Gerwick WH]]	+	[[Category: Alvarez, L H]]
-	[[Category: McKerrow JH]]	+	[[Category: Gerwick, W H]]
-	[[Category: Podust LM]]	+	[[Category: McKerrow, J H]]
-	[[Category: Sharma V]]	+	[[Category: Podust, L M]]
-	[[Category: Silva EB]]	+	[[Category: Sharma, V]]
		+	[[Category: Silva, E B]]
		+	[[Category: Cruzain]]
		+	[[Category: Cysteine protease]]
		+	[[Category: Gallinamide]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 06:19, 25 August 2021

OCA — Wed, 25 Aug 2021 06:19:06 GMT

←Older revision		Revision as of 06:19, 25 August 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7juj ~~is ON HOLD until Aug 19 2022~~	+	==Cruzain bound to Gallinamide inhibitor==
-		+	<StructureSection load='7juj' size='340' side='right'caption='[[7juj]]' scene=''>
-	~~Authors~~: ~~Silva, E~~.B.~~, Sharma, V~~., ~~Alvarez, L~~.H., ~~Gerwick~~, W.H., ~~McKerrow, J~~.H., ~~Podust, L~~.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JUJ FirstGlance]. <br>
-	~~Description: Cruzain bound to Gallinamide inhibitor~~	+	</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=7juj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7juj OCA], [https://pdbe.org/7juj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7juj RCSB], [https://www.ebi.ac.uk/pdbsum/7juj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7juj ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Mckerrow, J.H~~]]	+	__TOC__
-	[[Category: ~~Podust, L.M~~]]	+	</StructureSection>
-	[[Category: ~~Sharma, V~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Gerwick, W.H~~]]	+	[[Category: Alvarez LH]]
-	[[Category: ~~Silva, E.B~~]]	+	[[Category: Gerwick WH]]
-	[[Category: ~~Alvarez, L.H~~]]	+	[[Category: McKerrow JH]]
		+	[[Category: Podust LM]]
		+	[[Category: Sharma V]]
		+	[[Category: Silva EB]]

OCA at 19:05, 28 October 2020

OCA — Wed, 28 Oct 2020 19:05:57 GMT

←Older revision		Revision as of 19:05, 28 October 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7juj is ON HOLD	+	The entry 7juj is ON HOLD until Aug 19 2022

	Authors: Silva, E.B., Sharma, V., Alvarez, L.H., Gerwick, W.H., McKerrow, J.H., Podust, L.M.		Authors: Silva, E.B., Sharma, V., Alvarez, L.H., Gerwick, W.H., McKerrow, J.H., Podust, L.M.

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

OCA — Wed, 26 Aug 2020 09:42:57 GMT

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

←Older revision

Revision as of 09:42, 26 August 2020

OCA: New page: '''Unreleased structure''' The entry 7juj is ON HOLD Authors: Silva, E.B., Sharma, V., Alvarez, L.H., Gerwick, W.H., McKerrow, J.H., Podust, L.M. Description: Cruzain bound to Gallinam...

OCA — Wed, 26 Aug 2020 09:42:55 GMT

New page: '''Unreleased structure''' The entry 7juj is ON HOLD Authors: Silva, E.B., Sharma, V., Alvarez, L.H., Gerwick, W.H., McKerrow, J.H., Podust, L.M. Description: Cruzain bound to Gallinam...

New page

'''Unreleased structure'''

The entry 7juj is ON HOLD

Authors: Silva, E.B., Sharma, V., Alvarez, L.H., Gerwick, W.H., McKerrow, J.H., Podust, L.M.

Description: Cruzain bound to Gallinamide inhibitor
[[Category: Unreleased Structures]]
[[Category: Mckerrow, J.H]]
[[Category: Podust, L.M]]
[[Category: Sharma, V]]
[[Category: Gerwick, W.H]]
[[Category: Silva, E.B]]
[[Category: Alvarez, L.H]]