7jxt: Difference between revisions
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==Ovine COX-1 in complex with the subtype-selective derivative 2a== | |||
<StructureSection load='7jxt' size='340' side='right'caption='[[7jxt]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JXT 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]] 3.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=W8M:2-[4,5-bis(2-chlorophenyl)-1H-imidazol-2-yl]-6-(prop-2-en-1-yl)phenyl+methoxyacetate'>W8M</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=7jxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jxt OCA], [https://pdbe.org/7jxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jxt RCSB], [https://www.ebi.ac.uk/pdbsum/7jxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jxt ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The repertoire of natural products offers tremendous opportunities for chemical biology and drug discovery. Natural product-inspired synthetic molecules represent an ecologically and economically sustainable alternative to the direct utilization of natural products. De novo design with machine intelligence bridges the gap between the worlds of bioactive natural products and synthetic molecules. On employing the compound Marinopyrrole A from marine Streptomyces as a design template, the algorithm constructs innovative small molecules that can be synthesized in three steps, following the computationally suggested synthesis route. Computational activity prediction reveals cyclooxygenase (COX) as a putative target of both Marinopyrrole A and the de novo designs. The molecular designs are experimentally confirmed as selective COX-1 inhibitors with nanomolar potency. X-ray structure analysis reveals the binding of the most selective compound to COX-1. This molecular design approach provides a blueprint for natural product-inspired hit and lead identification for drug discovery with machine intelligence. | |||
Learning from Nature: From a Marine Natural Product to Synthetic Cyclooxygenase-1 Inhibitors by Automated De Novo Design.,Friedrich L, Cingolani G, Ko YH, Iaselli M, Miciaccia M, Perrone MG, Neukirch K, Bobinger V, Merk D, Hofstetter RK, Werz O, Koeberle A, Scilimati A, Schneider G Adv Sci (Weinh). 2021 Aug;8(16):e2100832. doi: 10.1002/advs.202100832. Epub 2021 , Jun 27. PMID:34176236<ref>PMID:34176236</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Cingolani | <div class="pdbe-citations 7jxt" style="background-color:#fffaf0;"></div> | ||
[[Category: Ko | |||
[[Category: | ==See Also== | ||
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Cingolani G]] | |||
[[Category: Friedrich L]] | |||
[[Category: Iaselli M]] | |||
[[Category: Ko Y]] | |||
[[Category: Miciaccia M]] | |||
[[Category: Schneider G]] | |||
[[Category: Scilimati A]] | |||