Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation

被引：52

作者：

Joubert, BM

Hua, L

Matsuda, SPT

机构：

[1] Rice Univ, Dept Chem, Houston, TX 77005 USA

[2] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA

来源：

ORGANIC LETTERS | 2000年 / 2卷 / 03期

关键词：

D O I：

10.1021/ol9912940

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] Lanosterol synthase converts oxidosqualene to the tetracyclic sterol precursor lanosterol, The mutation experiments described here show that an active-site valine residue in lanosterol synthase contributes to cyclization control through steric effects. Mutating to smaller alanine or glycine residues allows formation of the monocyclic achilleol A, whereas the leucine and isoleucine mutants make exclusively lanosterol, The phenylalanine mutant is inactive.

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页码：339 / 341

页数：3

相关论文

共 24 条

[1] ENZYMATIC CYCLIZATION OF SQUALENE AND OXIDOSQUALENE TO STEROLS AND TRITERPENES [J].

ABE, I ;

ROHMER, M ;

PRESTWICH, GD .

CHEMICAL REVIEWS, 1993, 93 (06) :2189-2206

[2]

Ausubel F.A., 1999, CURRENT PROTOCOLS MO

[3] ACHILLEOL-A - A NEW MONOCYCLIC TRITERPENE SKELETON FROM ACHILLEA-ODORATA L [J].

BARRERO, AF ;

ALVAREZMANZANEDA, EJ ;

ALVAREZMANZANEDA, R .

TETRAHEDRON LETTERS, 1989, 30 (25) :3351-3352

[4] ISOLATION OF AN ARABIDOPSIS-THALIANA GENE ENCODING CYCLOARTENOL SYNTHASE BY FUNCTIONAL EXPRESSION IN A YEAST MUTANT LACKING LANOSTEROL SYNTHASE BY THE USE OF A CHROMATOGRAPHIC SCREEN [J].

COREY, EJ ;

MATSUDA, SPT ;

BARTEL, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11628-11632

[5] Molecular cloning of a Schizosaccharomyces pombe cDNA encoding lanosterol synthase and investigation of conserved tryptophan residues [J].

Corey, EJ ;

Matsuda, SPT ;

Baker, CH ;

Ting, AY ;

Cheng, HM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 219 (02) :327-331

[6] MOLECULAR-CLONING, CHARACTERIZATION, AND OVEREXPRESSION OF ERG7 THE SACCHAROMYCES-CEREVISIAE GENE ENCODING LANOSTEROL SYNTHASE [J].

COREY, EJ ;

MATSUDA, SPT ;

BARTEL, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (06) :2211-2215

[7] A new strategy for stereocontrol of cation-olefin cyclization. The first chemical emulation of the A/B-trans-9,10-syn-folding pathway of steroid biosynthesis from 2,3-oxidosqualene [J].

Corey, EJ ;

Wood, HB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (47) :11982-11983

[8] AN EXPERIMENTAL DEMONSTRATION OF THE STEREOCHEMISTRY OF ENZYMATIC CYCLIZATION OF 2,3-OXIDOSQUALENE TO THE PROTOSTEROL SYSTEM, FORERUNNER OF LANOSTEROL AND CHOLESTEROL [J].

COREY, EJ ;

VIRGIL, SC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (10) :4025-4026

[9]

Darr L. B., 1999, Plant Physiology, V121, P686

[10] H-1 AND C-13 NMR ASSIGNMENTS FOR LANOSTAN-3 BETA-OL DERIVATIVES - REVISED ASSIGNMENTS FOR LANOSTEROL [J].

EMMONS, GT ;

WILSON, WK ;

SCHROEPFER, GJ .

MAGNETIC RESONANCE IN CHEMISTRY, 1989, 27 (11) :1012-1024