TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093 -: Taxonomy, production, isolation, and biological activities

被引：245

作者：

Koguchi, Y ^{[1
]}

Kohno, J ^{[1
]}

Nishio, M ^{[1
]}

Takahashi, K ^{[1
]}

Okuda, T ^{[1
]}

Ohnuki, T ^{[1
]}

Komatsubara, S ^{[1
]}

机构：

[1] Tanabe Seiyaku Co Ltd, Dept Basic Technol, Discovery Res Lab, Toda, Saitama 3358505, Japan

来源：

JOURNAL OF ANTIBIOTICS | 2000年 / 53卷 / 02期

关键词：

D O I：

10.7164/antibiotics.53.105

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

In our course of screening for novel proteasome inhibitors, TMC-95A and its diastereomers, TMC-95B to D, were isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093. TMC-95A inhibited the chymotrypsin-like (ChT-L), trypsin-like (TL), and peptidylglutamyl-peptide hydrolyzing (PGPH) activities of 20S proteasome with IC50 values of 5.4nM, 200 nM, and 60 nM, respectively. TMC-95B inhibited these activities to the same extent as TMC-95A, while the inhibitory activities of TMC-95C and D were 20 to 150 times weaker than that of TMC-95A and B. TMC-95A did not inhibit m-calpain, cathepsin L, and trypsin at 30 mu M, suggesting its high selectivity for proteasome. Taxonomy of the producing strain is also described.

引用

页码：105 / 109

页数：5

共 19 条

[11] LACTACYSTIN, A NOVEL MICROBIAL METABOLITE, INDUCES NEURITOGENESIS OF NEUROBLASTOMA-CELLS [J].

OMURA, S ;

FUJIMOTO, T ;

OTOGURO, K ;

MATSUZAKI, K ;

MORIGUCHI, R ;

TANAKA, H ;

SASAKI, Y .

JOURNAL OF ANTIBIOTICS, 1991, 44 (01) :113-116

[12] Reactions of [C-14]-3,4-dichloroisocoumarin with subunits of pituitary and spleen multicatalytic proteinase complexes (proteasomes) [J].

Orlowski, M ;

Cardozo, C ;

Eleuteri, AM ;

Kohanski, R ;

Kam, CM ;

Powers, JC .

BIOCHEMISTRY, 1997, 36 (45) :13946-13953

[13] PITUITARY MULTICATALYTIC PROTEINASE COMPLEX - SPECIFICITY OF COMPONENTS AND ASPECTS OF PROTEOLYTIC ACTIVITY [J].

ORLOWSKI, M ;

MICHAUD, C .

BIOCHEMISTRY, 1989, 28 (24) :9270-9278

[14] THE UBIQUITIN-PROTEASOME PATHWAY IS REQUIRED FOR PROCESSING THE NF-KAPPA-B1 PRECURSOR PROTEIN AND THE ACTIVATION OF NF-KAPPA-B [J].

PALOMBELLA, VJ ;

RANDO, OJ ;

GOLDBERG, AL ;

MANIATIS, T .

CELL, 1994, 78 (05) :773-785

[15] INHIBITORS OF THE PROTEASOME BLOCK THE DEGRADATION OF MOST CELL-PROTEINS AND THE GENERATION OF PEPTIDES PRESENTED ON MHC CLASS-I MOLECULES [J].

ROCK, KL ;

GRAMM, C ;

ROTHSTEIN, L ;

CLARK, K ;

STEIN, R ;

DICK, L ;

HWANG, D ;

GOLDBERG, AL .

CELL, 1994, 78 (05) :761-771

[16] Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway [J].

Solomon, V ;

Baracos, V ;

Sarraf, P ;

Goldberg, AL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) :12602-12607

[17] Kinetic characterization of the chymotryptic activity of the 20S proteasome [J].

Stein, RL ;

Melandri, F ;

Dick, L .

BIOCHEMISTRY, 1996, 35 (13) :3899-3908

[18]

TANAKA K, 1986, J BIOL CHEM, V261, P5197

[19]

1973, MANUAL COLOR NAMES

← 1 2 →