Abstract
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 α-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 °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.
Keywords: Mutagenesis, Crystallization, DAAO genes, FAD cofactor, Dimerization
Current Protein & Peptide Science
Title: Engineering the Properties of D-Amino Acid Oxidases by a Rational and a Directed Evolution Approach
Volume: 8 Issue: 6
Author(s): Loredano Pollegioni, Silvia Sacchi, Laura Caldinelli, Angelo Boselli, Mirella S. Pilone, Luciano Piubelli and Gianluca Molla
Affiliation:
Keywords: Mutagenesis, Crystallization, DAAO genes, FAD cofactor, Dimerization
Abstract: 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 α-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 °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.
Export Options
About this article
Cite this article as:
Pollegioni Loredano, Sacchi Silvia, Caldinelli Laura, Boselli Angelo, Pilone S. Mirella, Piubelli Luciano and Molla Gianluca, Engineering the Properties of D-Amino Acid Oxidases by a Rational and a Directed Evolution Approach, Current Protein & Peptide Science 2007; 8 (6) . https://dx.doi.org/10.2174/138920307783018677
DOI https://dx.doi.org/10.2174/138920307783018677 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Juvenile Systemic Lupus Erythematosus
Current Pediatric Reviews Ethical and Policy Considerations in the Application of Pharmacogenomic Testing for Tardive Dyskinesia: Case Study of the Dopamine D3 Receptor
Current Pharmacogenomics and Personalized Medicine Diabetic Retinopathy: Current and New Treatment Options
Current Diabetes Reviews Withdrawal Notice: Pharmacological analysis of Cannabis sativa L.: A potent herbal plant
Mini-Reviews in Medicinal Chemistry Biomarker Approach Towards Rheumatoid Arthritis Treatment
Current Rheumatology Reviews Further Evaluation of the Neuropharmacological Determinants of the Antidepressant-Like Effects of Curcumin
CNS & Neurological Disorders - Drug Targets GABAergic Modulation in Diabetic Encephalopathy-Related Depression
Current Pharmaceutical Design Alteration of Structure and Aggregation of α-Synuclein by Familial Parkinson’s Disease Associated Mutations
Current Protein & Peptide Science GqPCR-mediated Signalling in the Spotlight: From Visualization Towards Dissection and Quantification
Current Pharmaceutical Biotechnology The Emerging Pharmacology of TRPM8 Channels: Hidden Therapeutic Potential Underneath a Cold Surface
Current Pharmaceutical Biotechnology Biomaterial and Mesenchymal Stem Cell for Articular Cartilage Reconstruction
Current Stem Cell Research & Therapy Incretins Yesterday, Pleiotropic Gastrointestinal Hormones Today:Glucagon-Like Peptide-1 (GLP-1) and Glucose-ependent Insulinotropic Polypeptide (GIP)
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Current Options in the Treatment of Mitochondrial Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems
Recent Patents on Anti-Cancer Drug Discovery Editorial (Thematic Issue: Targeting Phosphodiesterases (PDEs) for Treatment of CNS Diseases)
Current Pharmaceutical Design Patents and the Development on Polymer based Nanomaterial (PAMAM Dendrimer) for Biomedical Applications
Recent Patents on Biomedical Engineering (Discontinued) Anti-Oxidants in Parkinson’s Disease Therapy: A Critical Point of View
Current Neuropharmacology Theories and Treatment of Drug Dependency: A Neurochemical Perspective
Current Molecular Pharmacology Progressive Supranuclear Palsy: What Do We Know About it?
Current Medicinal Chemistry Perioperative Management of Obese Parturients
Current Women`s Health Reviews