Panepophenanthrin, from a mushroom strain, a novel inhibitor of the ubiquitin-activating enzyme.
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.
Sekizawa
Ryuichi
R
Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. sekryu@bikaken.or.jp
Ikeno
Souichi
S
Nakamura
Hikaru
H
Naganawa
Hiroshi
H
Matsui
Susumu
S
Iinuma
Hironobu
H
Takeuchi
Tomio
T
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
D017931:DNA Primers; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C468593:panepophenanthrin; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes