4y4d: Difference between revisions
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The | ==Endothiapepsin in complex with fragment B51== | ||
<StructureSection load='4y4d' size='340' side='right'caption='[[4y4d]], [[Resolution|resolution]] 1.27Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4y4d]] 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=4Y4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y4D 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]] 1.269Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CFF:CAFFEINE'>CFF</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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'>[https://proteopedia.org/fgij/fg.htm?mol=4y4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y4d OCA], [https://pdbe.org/4y4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y4d RCSB], [https://www.ebi.ac.uk/pdbsum/4y4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y4d ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. | |||
Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.,Huschmann FU, Linnik J, Sparta K, Uhlein M, Wang X, Metz A, Schiebel J, Heine A, Klebe G, Weiss MS, Mueller U Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):346-55. doi:, 10.1107/S2053230X16004623. Epub 2016 Apr 22. PMID:27139825<ref>PMID:27139825</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4y4d" style="background-color:#fffaf0;"></div> | ||
[[Category: Linnik | |||
[[Category: | ==See Also== | ||
[[Category: Weiss | *[[Pepsin|Pepsin]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cryphonectria parasitica]] | |||
[[Category: Large Structures]] | |||
[[Category: Huschmann FU]] | |||
[[Category: Linnik J]] | |||
[[Category: Mueller U]] | |||
[[Category: Weiss MS]] | |||
Latest revision as of 06:42, 21 November 2024
Endothiapepsin in complex with fragment B51Endothiapepsin in complex with fragment B51
Structural highlights
FunctionPublication Abstract from PubMedCrystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.,Huschmann FU, Linnik J, Sparta K, Uhlein M, Wang X, Metz A, Schiebel J, Heine A, Klebe G, Weiss MS, Mueller U Acta Crystallogr F Struct Biol Commun. 2016 May 1;72(Pt 5):346-55. doi:, 10.1107/S2053230X16004623. Epub 2016 Apr 22. PMID:27139825[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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