Document Detail

Engineering the properties of D-amino acid oxidases by a rational and a directed evolution approach.
MedLine Citation:
PMID:  18220846     Owner:  NLM     Status:  MEDLINE    
D-amino acid oxidase (DAAO) is a FAD-containing flavoprotein that dehydrogenates the D-isomer of amino acids to the corresponding imino acids, coupled with the reduction of FAD. The cofactor then reoxidizes on molecular oxygen and the imino acid hydrolyzes spontaneously to the alpha-keto acid and ammonia. In vitro DAAO displays broad substrate specificity, acting on several neutral and basic D-amino acids: the most efficient substrates are amino acids with hydrophobic side chains. D-aspartic acid and D-glutamic acid are not substrates for DAAO. Through the years, it has been the subject of a number of structural, functional and kinetic investigations. The most recent advances are represented by site-directed mutagenesis studies and resolution of the 3D-structure of the enzymes from pig, human and yeast. The two approaches have given us a deeper understanding of the structure-function relationships and promoted a number of investigations aimed at the modulating the protein properties. By a rational and/or a directed evolution approach, DAAO variants with altered substrate specificity (e.g., active on acidic or on all D-amino acids), increased stability (e.g., stable up to 60 degrees C), modified interaction with the flavin cofactor, and altered oligomeric state were produced. The aim of this paper is to provide an overview of the most recent research on the engineering of DAAOs to illustrate their new intriguing properties, which also have enabled us to pursue new biotechnological applications.
Loredano Pollegioni; Silvia Sacchi; Laura Caldinelli; Angelo Boselli; Mirella S Pilone; Luciano Piubelli; Gianluca Molla
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current protein & peptide science     Volume:  8     ISSN:  1389-2037     ISO Abbreviation:  Curr. Protein Pept. Sci.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2008-01-28     Completed Date:  2008-02-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100960529     Medline TA:  Curr Protein Pept Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  600-18     Citation Subset:  IM    
Department of Biotechnology and Molecular Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy.
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MeSH Terms
Amino Acid Sequence
D-Amino-Acid Oxidase / chemistry*,  genetics,  metabolism*
Directed Molecular Evolution / methods*
Enzyme Stability
Molecular Sequence Data
Protein Engineering / methods*
Structure-Activity Relationship
Substrate Specificity
Reg. No./Substance:
EC Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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