title: Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain.
abstract: The crystal structures of two hydroxymethyl ketone inhibitors complexed to the cysteine protease cruzain have been determined at 1.1 and 1.2 A resolution, respectively. These high resolution crystal structures provide the first structures of non-covalent inhibitors bound to cruzain. A series of compounds were prepared and tested based upon the structures providing further insight into the key binding interactions.
authors.affiliation: Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley 94720, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Huang
authors.forename: Linda S
authors.initials: LS
authors.lastname: Brinen
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ellman
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007659:Ketones; D015800:Protozoan Proteins; D013438:Sulfhydryl Compounds; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi