9fzv: Difference between revisions
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==Structure of cathepsin B1 from Schistosoma mansoni (SmCB1) in complex with a carborane inhibitor== | |||
<StructureSection load='9fzv' size='340' side='right'caption='[[9fzv]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9fzv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FZV 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=9fzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fzv OCA], [https://pdbe.org/9fzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fzv RCSB], [https://www.ebi.ac.uk/pdbsum/9fzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fzv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8MNY2_SCHMA Q8MNY2_SCHMA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The closo-1,2-C(2)B(10)H(12) carborane is a recognized 3D aromatic icosahedral building block, with an electron distribution governed by the outer hydridic BH and acidic CH vertices. We attached the carborane cage to a peptidomimetic scaffold to generate an active-site inhibitor of SmCB1, a protease drug target in the Schistosoma pathogen. The carborane-tagged compound exhibited superior inhibitor affinity and bioactivity compared to its conventional 2D aromatic phenyl analog. Quantum mechanical computations, based on the crystal structure of the protease-inhibitor complex, revealed that the carborane tag contributed to inhibitor binding not only through nonpolar interactions but also via a key hydrogen bond between its CH vertex and a negatively charged residue in the binding site. This interaction, driven by the large dipole moment of the carborane cage, resulted in a more favorable energy contribution than that of the phenyl group in the 2D analog. The carborane pharmacophore boosted affinity for SmCB1 and conferred specific anti-schistosomal activity, highlighting its potential in protein ligand design. | |||
Fat or flat? The impact of dipole moment vectors on non-covalent interactions between aromatic tags and macromolecules.,Holub J, Jilkova A, Lemke C, Cianni L, Spiwokova P, Horn M, Breuer C, Leontovyc A, Brynda J, Mertlikova-Kaiserova H, Chanova M, Dos Reis Rocho F, Montanari CA, El-Sakkary N, Caffrey CR, Gutschow M, Hnyk D, Mares M, Fanfrlik J Inorg Chem Front. 2025 Oct 21. doi: 10.1039/d5qi01546d. PMID:41127420<ref>PMID:41127420</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9fzv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Schistosoma mansoni]] | |||
[[Category: Brynda J]] | |||
[[Category: Fanfrlik J]] | |||
[[Category: Guetschow M]] | |||
[[Category: Holub J]] | |||
[[Category: Horn M]] | |||
[[Category: Jilkova A]] | |||
[[Category: Mares M]] | |||
[[Category: Spiwokova P]] | |||
Latest revision as of 07:11, 29 October 2025
Structure of cathepsin B1 from Schistosoma mansoni (SmCB1) in complex with a carborane inhibitor
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