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Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family.
- Source :
-
Chemistry & biology [Chem Biol] 2006 Dec; Vol. 13 (12), pp. 1317-26. - Publication Year :
- 2006
-
Abstract
- Tyrosine ammonia-lyase (TAL) is a recently described member of the aromatic amino acid lyase family, which also includes phenylalanine (PAL) and histidine ammonia-lyases (HAL). TAL is highly selective for L-tyrosine, and synthesizes 4-coumaric acid as a protein cofactor or antibiotic precursor in microorganisms. In this report, we identify a single active site residue important for substrate selection in this enzyme family. Replacing the active site residue His89 with Phe in TAL completely switched its substrate selectivity from tyrosine to phenylalanine, thereby converting it into a highly active PAL. When a corresponding mutation was made in PAL, the enzyme lost PAL activity and gained TAL activity. The discovered substrate selectivity switch is a rare example of a complete alteration of substrate specificity by a single point mutation. We also show that the identity of the amino acid at the switch position can serve as a guide to predict substrate specificities of annotated aromatic amino acid lyases in genome sequences.
- Subjects :
- Amino Acid Sequence
Amino Acids, Aromatic metabolism
Ammonia-Lyases metabolism
Bacteria enzymology
Binding Sites
Cells, Cultured
Models, Molecular
Molecular Sequence Data
Mutation
Sequence Alignment
Substrate Specificity
Amino Acids, Aromatic chemistry
Ammonia-Lyases chemistry
Ammonia-Lyases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1074-5521
- Volume :
- 13
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Chemistry & biology
- Publication Type :
- Academic Journal
- Accession number :
- 17185227
- Full Text :
- https://doi.org/10.1016/j.chembiol.2006.10.008