PMID: 8597586Feb 16, 1996Paper

Mechanism and structural requirements for transformation of substrates by the (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase from Saccharomyces cerevisiae

Biochimica Et Biophysica Acta
M VenkatrameshW D Nes

Abstract

The mechanism of action and active site of the enzyme (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase (SMT) from Saccharomyces cerevisiae strain GL7 have been probed with AdoMet, (S)-adenosyl-L-homocysteine, a series of 35 sterol substrates as acceptor molecules and a series of 10 substrate and high energy intermediate (HEI) sterol analogues as inhibitors of biomethylation. The SMT was found to be selective for sterol, both regio- and stereochemically. The presence of an unhindered 24,25-bond, an equatorially-oriented polar group at C-3 (which must act as a proton acceptor) attached to a planar nucleus and a freely rotating side chain were obligatory structural features for sterol binding/catalysis; no essential requirement or significant harmful effects could be found for the introduction of an 8(9)-bond, 14 alpha-methyl or 9 beta,19-cyclopropyl group. Alternatively, methyl groups at C-4 prevented productive sterol binding to the SMT. Initial velocity, product inhibition, and dead-end experiments demonstrated a rapid-equilibrium random bi bi mechanism. Deuterium isotope effects developed from SMT assays containing mixtures of [3-3H]zymosterol with AdoMet or [methyl-2H3]AdoMet confirmed the operation of a rando...Continue Reading

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Citations

Aug 30, 2003·Phytochemistry·W David Nes
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·A BellamineM R Waterman
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·B RuanG J Schroepfer
Jul 27, 2004·Antimicrobial Agents and Chemotherapy·Silvia Orenes LorenteIan H Gilbert
Oct 16, 2010·Archives of Biochemistry and Biophysics·Kulothungan GanapathyW David Nes
Nov 19, 2003·Archives of Biochemistry and Biophysics·Wenxu Zhou, W David Nes
Nov 17, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wenxu ZhouW David Nes
Aug 28, 2002·The Journal of Biological Chemistry·W David NesPruthvi Jayasimha
Jun 17, 2003·The Journal of Biological Chemistry·W David NesMatthew B Miller
May 1, 1997·Bioorganic & Medicinal Chemistry·A P Acuna-JohnsonE K Czyzewska
Sep 10, 2011·Chemical Reviews·W David Nes
Oct 8, 2021·Planta·Yiyang ChenXiaowei Du

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