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Titolo:
Effects of modification of the hydrophobic C-1-C-16 segment of tautomycin on its affinity to type-1 and type-2A protein phosphatases
Autore:
Takai, A; Tsuboi, K; Koyasu, M; Isobe, M;
Indirizzi:
Nagoya Univ, Grad Sch Med, Lab Biomol Dynam, Showa Ku, Nagoya, Aichi 4668055, Japan Nagoya Univ Nagoya Aichi Japan 4668055 a Ku, Nagoya, Aichi 4668055, Japan Nagoya Univ, Grad Sch Bioagr Sci, Bioorgan Chem Lab, Nagoya, Aichi 4648601, Japan Nagoya Univ Nagoya Aichi Japan 4648601 Lab, Nagoya, Aichi 4648601, Japan
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 350, anno: 2000,
parte:, 1
pagine: 81 - 88
SICI:
0264-6021(20000815)350:<81:EOMOTH>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE MYOSIN; OKADAIC ACID; INHIBITION ASSAY; MICROCYSTIN-LR; SPONGE TOXIN; CALYCULIN-A; BINDING; SPECIFICITY; ISOFORMS; ENZYME;
Keywords:
enantiomer; enzyme inhibitor; okadaic acid; structure-affinity relationship;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Takai, A Nagoya Univ, Grad Sch Med, Lab Biomol Dynam, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668055, Japan Nagoya Univ 65 Tsurumai Cho Nagoya Aichi Japan 4668055 055, Japan
Citazione:
A. Takai et al., "Effects of modification of the hydrophobic C-1-C-16 segment of tautomycin on its affinity to type-1 and type-2A protein phosphatases", BIOCHEM J, 350, 2000, pp. 81-88

Abstract

Among the naturally occurring toxins that are known to have specific inhibitory effects on type-1 and type-2A protein phosphatases (PP1 and PP2A), tautomycin (TM) is unique in that it exhibits significantly higher affinity to PP1 than to PP2A. The ratio of the dissociation constant for the PP1-TM interaction to that for the PP2A-TM interaction (the PP1/PP2A ratio) is 0.01-0.03. The aim of the present study was to evaluate the possible contributions of the C-1-C-16 segment of TM to the affinity characteristics of the toxin. The relatively hydrophobic segment contains a spiroketal motif whose enantiomeric form is present in okadaic acid (OA), which exhibits exceedingly higher affinity to PP2A than to PP1. We therefore synthesized two TM analogues: TM1 in which the side chains of the spiroketal motif of TM were removed but its absolute configuration was retained, and TM2 in which the spiroketal motif of TM1 was replaced with its enantiomeric form. The effects of TM, TM1 and TM2 on the activities of the native catalytic subunits of PP1 (PP1C) and PP2A and a recombinant gamma isoform of PP1 (PP1 gamma) were examined. The PP1/PP2A ratio determined thereby was 0.2-0.5 for TM1 and 5-10 for TM2. Both the presence of the side chains and the stereochemistry of the spiroketal moieties may be major determining factors for the affinity characteristics of TM. We also show that a monoclonal antibody raised against OAbinds to TM2 albeit with much lower affinity than to OA, whereas it exhibits no measurable affinities to TM and TM1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 21:39:59