title: Panepophenanthrin, from a mushroom strain, a novel inhibitor of the ubiquitin-activating enzyme.
abstract: Screening for inhibitors of the ubiquitin-proteasome pathway, considered to regulate important cellular events and linked to serious diseases as well, led to isolation of a new compound, panepophenanthrin, from the fermented broth of a mushroom strain, Panus rudis Fr. IFO 8994. This is the first inhibitor of the ubiquitin-activating enzyme, which is indispensable for the ubiquitin-proteasome pathway. The structure of panepophenanthrin was determined by NMR and X-ray crystallographic analyses as 1,3a,10-trihydroxy-10c-(3-hydroxy-3-methylbut-1-enyl)-5,5-dimethyl-1,2,3,3a,5,5a,8,9,10,10a,10b,10c-dodecahydro-4-oxa-2,3,8,9-diepoxyacephenanthrylen-7-one.
authors.affiliation: Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. sekryu@bikaken.or.jp
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sekizawa
authors.forename: Souichi
authors.initials: S
authors.lastname: Ikeno
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naganawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Matsui
authors.forename: Hironobu
authors.initials: H
authors.lastname: Iinuma
authors.forename: Tomio
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D001483:Base Sequence; D018360:Crystallography, X-Ray; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008025:Ligases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C468593:panepophenanthrin; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes