MECHANISM-BASED ACTIVE-SITE MODIFICATION OF STEROL METHYL TRANSFERASEBY TRITIUM-LABELED 26-HOMOCHOLESTA-8,14,24-TRIEN-26-YN-3-BETA-OL

Authors
NES WD MARSHALL JA ZHOU W HE L DENNIS AL
Citation
Wd. Nes et al., MECHANISM-BASED ACTIVE-SITE MODIFICATION OF STEROL METHYL TRANSFERASEBY TRITIUM-LABELED 26-HOMOCHOLESTA-8,14,24-TRIEN-26-YN-3-BETA-OL, Tetrahedron letters, 39(47), 1998, pp. 8575-8578
Citations number
16
Categorie Soggetti
Chemistry Inorganic & Nuclear
Journal title
Tetrahedron letters → ACNP
ISSN journal
00404039
Volume
39
Issue
47
Year of publication
1998
Pages
8575 - 8578
Database
ISI
SICI code
0040-4039(1998)39:47<8575:MAMOSM>2.0.ZU;2-0
Abstract
The title compound (26-HC, 5) was synthesized and tested as a mechanis m-based inhibitor of the sterol methyl transferase (SMT) enzyme from S accharomyces cerevisiae. Enzyme assays were performed with SMT enzyme using zymosterol as substrate and AdoMet as coenzyme. The inhibition o f SMT enzyme by 26-HC showed an apparent k(i) of 72.5 mu M and k(inact ) of 2.4 min(-1) Covalent modification of the active site of a SMT enz yme was demonstrated for the first time using [3-H-3]26-HC. (C) 1998 E lsevier Science Ltd. All rights reserved.