5j25 - Revision history

OCA at 10:42, 6 September 2023

OCA — Wed, 06 Sep 2023 10:42:48 GMT

←Older revision		Revision as of 10:42, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='5j25' size='340' side='right'caption='[[5j25]], [[Resolution\|resolution]] 1.24Å' scene=''>		<StructureSection load='5j25' size='340' side='right'caption='[[5j25]], [[Resolution\|resolution]] 1.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j25]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4y4c 4y4c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J25 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5J25 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j25]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4y4c 4y4c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J25 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=47K:2-(4-METHYLPIPERIDIN-1-YL)-N-[3-(PROPAN-2-YL)-1,2-OXAZOL-5-YL]ACETAMIDE'>47K</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.24Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=47K:2-(4-METHYLPIPERIDIN-1-YL)-N-[3-(PROPAN-2-YL)-1,2-OXAZOL-5-YL]ACETAMIDE'>47K</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j25 OCA], [~~http~~://pdbe.org/5j25 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5j25 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5j25 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5j25 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=5j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j25 OCA], [https://pdbe.org/5j25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j25 RCSB], [https://www.ebi.ac.uk/pdbsum/5j25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j25 ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA]
-	~~Druglike molecules are defined by Lipinski's rule of 5, to characterize fragment thresholds, they have been reduced from 5 to 3 (Astex's rule of 3)~~. ~~They are applied to assemble fragment libraries, and providers use them to select fragments for commercial offer~~. We question whether these rules are too stringent to compose fragment libraries with candidates exhibiting sufficient room for chemical subsequent growing and merging modifications as appropriate functional groups for chemical transformations are required. Usually these groups exhibit properties as hydrogen bond donors/acceptors and provide entry points for optimization chemistry. We therefore designed a fragment library (364 entries) without strictly applying the rule of 3. For initial screening for endothiapepsin binding, we performed a biochemical cleavage assay of a fluorogenic substrate at 1 mM. "Hits" were defined to inhibit the enzyme by at least 40%. Fifty-five hits were suggested and subsequently soaked into endothiapepsin crystals. Eleven crystal structures could be determined covering fragments with diverse binding modes: (i) direct binding to the catalytic dyad aspartates, (ii) water-mediated binding to the aspartates, (iii) no direct interaction with the dyad. They occupy different specificity pockets. Only 4 of the 11 fragments are consistent with the rule of 3. Restriction to this rule would have limited the fragment hits to a strongly reduced variety of chemotypes.	+

-	A Small Nonrule of 3 Compatible Fragment Library Provides High Hit Rate of Endothiapepsin Crystal Structures with Various Fragment Chemotypes.,Koster H, Craan T, Brass S, Herhaus C, Zentgraf M, Neumann L, Heine A, Klebe G J Med Chem. 2011 Oct 25. PMID:21972967<ref>PMID:21972967</ref>	+	==See Also==
-		+	*[[Pepsin\|Pepsin]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5j25" style="background-color:#fffaf0;"></div>~~	+
-	== ~~References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Cryphonectria parasitica]]		[[Category: Cryphonectria parasitica]]
-	[[Category: Endothiapepsin]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Heine, A]]	+	[[Category: Heine A]]
-	[[Category: Klebe, G]]	+	[[Category: Klebe G]]
-	[[Category: Krimmer~~, S G]]~~	+	[[Category: Krimmer SG]]
-	~~[[Category: Fragment screening]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibition~~]]	+

OCA at 07:25, 10 June 2020

OCA — Wed, 10 Jun 2020 07:25:23 GMT

←Older revision		Revision as of 07:25, 10 June 2020
Line 1:		Line 1:

	==Endothiapepsin in complex with fragment 158==		==Endothiapepsin in complex with fragment 158==
-	<StructureSection load='5j25' size='340' side='right' caption='[[5j25]], [[Resolution\|resolution]] 1.24Å' scene=''>	+	<StructureSection load='5j25' size='340' side='right'caption='[[5j25]], [[Resolution\|resolution]] 1.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j25]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4y4c 4y4c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J25 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5J25 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j25]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4y4c 4y4c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J25 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J25 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=47K:2-(4-METHYLPIPERIDIN-1-YL)-N-[3-(PROPAN-2-YL)-1,2-OXAZOL-5-YL]ACETAMIDE'>47K</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=47K:2-(4-METHYLPIPERIDIN-1-YL)-N-[3-(PROPAN-2-YL)-1,2-OXAZOL-5-YL]ACETAMIDE'>47K</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </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=5j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j25 OCA], [http://pdbe.org/5j25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j25 RCSB], [http://www.ebi.ac.uk/pdbsum/5j25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j25 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j25 OCA], [http://pdbe.org/5j25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j25 RCSB], [http://www.ebi.ac.uk/pdbsum/5j25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j25 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 23:		Line 23:
	[[Category: Cryphonectria parasitica]]		[[Category: Cryphonectria parasitica]]
	[[Category: Endothiapepsin]]		[[Category: Endothiapepsin]]
		+	[[Category: Large Structures]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
	[[Category: Klebe, G]]		[[Category: Klebe, G]]

OCA at 13:16, 5 April 2017

OCA — Wed, 05 Apr 2017 13:16:19 GMT

←Older revision		Revision as of 13:16, 5 April 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5j25 is ~~ON HOLD until Paper~~ Publication	+	==Endothiapepsin in complex with fragment 158==
		+	<StructureSection load='5j25' size='340' side='right' caption='[[5j25]], [[Resolution\|resolution]] 1.24Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5j25]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4y4c 4y4c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J25 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=47K:2-(4-METHYLPIPERIDIN-1-YL)-N-[3-(PROPAN-2-YL)-1,2-OXAZOL-5-YL]ACETAMIDE'>47K</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </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=5j25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j25 OCA], [http://pdbe.org/5j25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j25 RCSB], [http://www.ebi.ac.uk/pdbsum/5j25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j25 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Druglike molecules are defined by Lipinski's rule of 5, to characterize fragment thresholds, they have been reduced from 5 to 3 (Astex's rule of 3). They are applied to assemble fragment libraries, and providers use them to select fragments for commercial offer. We question whether these rules are too stringent to compose fragment libraries with candidates exhibiting sufficient room for chemical subsequent growing and merging modifications as appropriate functional groups for chemical transformations are required. Usually these groups exhibit properties as hydrogen bond donors/acceptors and provide entry points for optimization chemistry. We therefore designed a fragment library (364 entries) without strictly applying the rule of 3. For initial screening for endothiapepsin binding, we performed a biochemical cleavage assay of a fluorogenic substrate at 1 mM. "Hits" were defined to inhibit the enzyme by at least 40%. Fifty-five hits were suggested and subsequently soaked into endothiapepsin crystals. Eleven crystal structures could be determined covering fragments with diverse binding modes: (i) direct binding to the catalytic dyad aspartates, (ii) water-mediated binding to the aspartates, (iii) no direct interaction with the dyad. They occupy different specificity pockets. Only 4 of the 11 fragments are consistent with the rule of 3. Restriction to this rule would have limited the fragment hits to a strongly reduced variety of chemotypes.

-	~~Authors: Krimmer~~, S~~.G.~~, ~~Heine~~, A., Klebe, G.	+	A Small Nonrule of 3 Compatible Fragment Library Provides High Hit Rate of Endothiapepsin Crystal Structures with Various Fragment Chemotypes.,Koster H, Craan T, Brass S, Herhaus C, Zentgraf M, Neumann L, Heine A, Klebe G J Med Chem. 2011 Oct 25. PMID:21972967<ref>PMID:21972967</ref>

-	~~Description~~: ~~Endothiapepsin in complex with fragment 158~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Krimmer, S.G~~]]	+	<div class="pdbe-citations 5j25" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cryphonectria parasitica]]
		+	[[Category: Endothiapepsin]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
	[[Category: Klebe, G]]		[[Category: Klebe, G]]
		+	[[Category: Krimmer, S G]]
		+	[[Category: Fragment screening]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibition]]

OCA at 09:45, 9 March 2017

OCA — Thu, 09 Mar 2017 09:45:31 GMT

←Older revision		Revision as of 09:45, 9 March 2017
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Krimmer, S.G]]		[[Category: Krimmer, S.G]]
-	[[Category: Klebe, G]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
		+	[[Category: Klebe, G]]

OCA at 13:03, 1 June 2016

OCA — Wed, 01 Jun 2016 13:03:17 GMT

←Older revision		Revision as of 13:03, 1 June 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5j25 is ON HOLD	+	The entry 5j25 is ON HOLD until Paper Publication

	Authors: Krimmer, S.G., Heine, A., Klebe, G.		Authors: Krimmer, S.G., Heine, A., Klebe, G.

OCA: Protected "5j25" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 01:20:28 GMT

Protected "5j25" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:20, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5j25 is ON HOLD Authors: Krimmer, S.G., Heine, A., Klebe, G. Description: Endothiapepsin in complex with fragment 158 [[Category: Unreleased Struct...

OCA — Wed, 11 May 2016 01:20:26 GMT

New page: '''Unreleased structure''' The entry 5j25 is ON HOLD Authors: Krimmer, S.G., Heine, A., Klebe, G. Description: Endothiapepsin in complex with fragment 158 [[Category: Unreleased Struct...

New page

'''Unreleased structure'''

The entry 5j25 is ON HOLD

Authors: Krimmer, S.G., Heine, A., Klebe, G.

Description: Endothiapepsin in complex with fragment 158
[[Category: Unreleased Structures]]
[[Category: Krimmer, S.G]]
[[Category: Klebe, G]]
[[Category: Heine, A]]