title: The structure of endothiapepsin complexed with a Phe-Tyr reduced-bond inhibitor at 1.35 Å resolution.
abstract: Endothiapepsin is a typical member of the aspartic proteinase family. The catalytic mechanism of this family is attributed to two conserved catalytic aspartate residues, which coordinate the hydrolysis of a peptide bond. An oligopeptide inhibitor (IC50 = 0.62 µM) based on a reduced-bond transition-state inhibitor of mucorpepsin was co-crystallized with endothiapepsin and the crystal structure of the enzyme-inhibitor complex was determined at 1.35 Å resolution. A total of 12 hydrogen bonds between the inhibitor and the active-site residues were identified. The resulting structure demonstrates a number of novel subsite interactions in the active-site cleft.
authors.affiliation: Laboratory of Protein Crystallography, Centre for Amyloidosis and Acute Phase Proteins, UCL Division of Medicine (Royal Free Campus), Rowland Hill Street, London NW3 2PF, England.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Laboratory of Protein Crystallography, Centre for Amyloidosis and Acute Phase Proteins, UCL Division of Medicine (Royal Free Campus), Rowland Hill Street, London NW3 2PF, England.
authors.forename: J B
authors.initials: JB
authors.lastname: Cooper
authors.affiliation: Laboratory of Protein Crystallography, Centre for Amyloidosis and Acute Phase Proteins, UCL Division of Medicine (Royal Free Campus), Rowland Hill Street, London NW3 2PF, England.
authors.forename: S P
authors.initials: SP
authors.lastname: Wood
mesh_terms: D001203:Ascomycota / Q000201:enzymology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006860:Hydrogen Bonding / Q000187:drug effects; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004151:Dipeptides; D011480:Protease Inhibitors; C473904:phenylalanine-1-tyrosine; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase
keywords: aspartic proteases; endothiapepsin; inhibitor; transition state