3pm4: Difference between revisions

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-[[Image:3pm4.jpg|left|200px]]
-<!--
+==Endothiapepsin in complex with a fragment==
-The line below this paragraph, containing "STRUCTURE_3pm4", creates the "Structure Box" on the page.
+<StructureSection load='3pm4' size='340' side='right'caption='[[3pm4]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3pm4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PM4 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F5N:2-(IMIDAZO[1,2-A]PYRIDIN-2-YL)-N-PHENYLACETAMIDE'>F5N</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-{{STRUCTURE_3pm4|  PDB=3pm4  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pm4 OCA], [https://pdbe.org/3pm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pm4 RCSB], [https://www.ebi.ac.uk/pdbsum/3pm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pm4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA]
+<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.
-===Endothiapepsin in complex with a fragment===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3pm4" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_21972967}}, adds the Publication Abstract to the page
+*[[Pepsin|Pepsin]]
-(as it appears on PubMed at http://www.pubmed.gov), where 21972967 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_21972967}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3pm4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PM4 OCA].
-==Reference==
-<ref group="xtra">PMID:021972967</ref><references group="xtra"/>
 [[Category: Cryphonectria parasitica]]
-[[Category: Endothiapepsin]]
+[[Category: Large Structures]]
-[[Category: Heine, A.]]
+[[Category: Heine A]]
-[[Category: Klebe, G.]]
+[[Category: Klebe G]]
-[[Category: Koester, H.]]
+[[Category: Koester H]]
-[[Category: Hydrolase]]