A Single Residue Influences the Reaction Mechanism of Ammonia Lyases and Mutases

被引：40

作者：

Bartsch, Sebastian ^{[1
]}

Bornscheuer, Uwe T. ^{[1
]}

机构：

[1] Ernst Moritz Arndt Univ Greifswald, Dept Biotechnol & Enzyme Catalysis, Inst Biochem, D-17487 Greifswald, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2009年 / 48卷 / 18期

关键词：

enzyme catalysis; Friedel-Crafts mechanism; lyases; molecular modeling; substrate specificity; SUBSTRATE-SPECIFICITY; PHENYLALANINE; DEHYDROALANINE; CATALYSIS; MODEL;

D O I：

10.1002/anie.200900337

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

All ways lead to Rome? Computer modeling and kinetic measurements identified a distinct residue in Phe/Tyr ammonia lyases (PAL/TAL) which controls whether the Friedel-Crafts or an E1cB reaction mechanism takes place. Hence, Glu484 in pcPAL favors the Friedel-Crafts reaction (see picture, MIO=4-methylidene imidazol-5-one) whereas an Asn in TAL gives an elimination reaction. These mechanistic investigations also reveal activity of a PAL mutant and a TAL towards an amino alcohol. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：3362 / 3365

页数：4

共 20 条

[1]

Bornscheuer U. T., 2004, ANGEW CHEM, V116, P6156

[2] The mechanism of MIO-based aminomutases in β-amino acid biosynthesis [J].

Christianson, Carl V. ;

Montavon, Timothy J. ;

Festin, Grace M. ;

Cooke, Heather A. ;

Shen, Ben ;

Bruner, Steven D. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (51) :15744-+

[3] The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway [J].

Christianson, Carl V. ;

Montavon, Timothy J. ;

Van Lanen, Steven G. ;

Shen, Ben ;

Bruner, Steven D. .

BIOCHEMISTRY, 2007, 46 (24) :7205-7214

[4]

Gloge A, 2000, CHEM-EUR J, V6, P3386, DOI 10.1002/1521-3765(20000915)6:18<3386::AID-CHEM3386>3.0.CO

[5]

2-5

[6] L-PHENYLALANINE AMMONIA-LYASE .4. EVIDENCE THAT PROSTHETIC GROUP CONTAINS A DEHYDROALANYL RESIDUE AND MECHANISM OF ACTION [J].

HANSON, KR ;

HAVIR, EA .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1970, 141 (01) :1-+

[7] USE OF N-15 AND DEUTERIUM-ISOTOPE EFFECTS TO DETERMINE THE CHEMICAL MECHANISM OF PHENYLALANINE AMMONIA-LYASE [J].

HERMES, JD ;

WEISS, PM ;

CLELAND, WW .

BIOCHEMISTRY, 1985, 24 (12) :2959-2967

[8] THE ROLE OF DEHYDROALANINE IN CATALYSIS BY HISTIDINE AMMONIA-LYASE [J].

LANGER, M ;

PAULING, A ;

RETEY, J .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1995, 34 (13-14) :1464-1465

[9] Structural determinants and modulation of substrate specificity in phenylalanine-tyrosine ammonia-lyases [J].

Louie, Gordon V. ;

Bowman, Marianne E. ;

Moffitt, Michelle C. ;

Baiga, Thomas J. ;

Moore, Bradley S. ;

Noel, Joseph P. .

CHEMISTRY & BIOLOGY, 2006, 13 (12) :1327-1338

[10] Friedel-Crafts-type mechanism for the enzymatic elimination of ammonia from histicline and phenylalanine [J].

Poppe, L ;

Rétey, J .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (24) :3668-3688

← 1 2 →