5o7e

Crystal structure of the peptidase domain of collagenase H from Clostridium histolyticum in complex with N-aryl mercaptoacetamide-based inhibitorCrystal structure of the peptidase domain of collagenase H from Clostridium histolyticum in complex with N-aryl mercaptoacetamide-based inhibitor

Structural highlights 5o7e is a 1 chain structure with sequence from "bacillus_histolyticus"_weinberg_and_seguin_1916 "bacillus histolyticus" weinberg and seguin 1916. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Related: 4arf Gene: colH ("Bacillus histolyticus" Weinberg and Seguin 1916) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Secreted virulence factors like bacterial collagenases are conceptually attractive targets for fighting microbial infections. However, previous attempts to develop potent compounds against these metalloproteases failed to achieve selectivity against human matrix metalloproteinases (MMPs). Using a surface plasmon resonance-based screening complemented with enzyme inhibition assays, we discovered an N-aryl mercaptoacetamide-based inhibitor scaffold that showed sub-micromolar affinities toward collagenase H (ColH) from the human pathogen Clostridium histolyticum. Moreover, these inhibitors also efficiently blocked the homologous bacterial collagenases, ColG from C. histolyticum, ColT from C. tetani, and ColQ1 from the Bacillus cereus strain Q1, while showing negligible activity toward human MMPs-1, -2, -3, -7, -8, and -14. The most active compound displayed a more than 1000-fold selectivity over human MMPs. This selectivity can be rationalized by the crystal structure of ColH with this compound, revealing a distinct non-primed binding mode to the active site. The non-primed binding mode presented here paves the way for the development of selective broad-spectrum bacterial collagenase inhibitors with potential therapeutic application in humans. Discovery of a Potent Inhibitor Class with High Selectivity toward Clostridial Collagenases.,Schonauer E, Kany AM, Haupenthal J, Husecken K, Hoppe IJ, Voos K, Yahiaoui S, Elsasser B, Ducho C, Brandstetter H, Hartmann RW J Am Chem Soc. 2017 Sep 13;139(36):12696-12703. doi: 10.1021/jacs.7b06935. Epub, 2017 Aug 31. PMID:28820255 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Collagenase 3D structures Transcription initiation factor

spinqualitylabelsall models 5o7e, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image