5mae

<StructureSection load='5mae' size='340' side='right' caption='[[5mae]], [[Resolution|resolution]] 1.00&Aring;' scene=''>

<table><tr><td colspan='2'>[[5mae]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MAE FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KN:[4-[CYCLOPENTYL(PYRAZIN-2-YLMETHYL)AMINO]-6-MORPHOLIN-4-YL-1,3,5-TRIAZIN-2-YL]METHYLIDENEAZANIDE'>7KN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_L Cathepsin L], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.15 3.4.22.15] </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=5mae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mae OCA], [http://pdbe.org/5mae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mae RCSB], [http://www.ebi.ac.uk/pdbsum/5mae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mae ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/CATL1_HUMAN CATL1_HUMAN]] Important for the overall degradation of proteins in lysosomes.

We report an extensive "heteroarene scan" of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate pi-stacking on the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket. This heteroarenepeptide bond stacking was supported by a co-crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki ) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the orientation of the local dipole moments of heteroarene and peptide bond could not be confirmed. Binding of benzothienyl (Ki =4 nm) and benzothiazolyl (Ki =17 nm) ligands was enhanced by intermolecular C-SO=C interactions (chalcogen bonding) with the backbone C=O of Asn66 in the S3 pocket. The ligands were also tested for the related enzyme rhodesain.

 

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== References ==

[[Category: Cathepsin L]]

[[Category: Benz, J]]

[[Category: Kuglstatter, A]]

[[Category: Stihle, M]]

[[Category: Hydrolase]]

[[Category: Protease inhibitor]]