Biochemical Properties of Human D-Amino Acid Oxidase
D-amino acid oxidase catalyzes the oxidative deamination of D-amino acids. In the brain, the NMDA receptor coagonist D-serine has been proposed as its physiological substrate. In order to shed light on the mechanisms regulating D-serine concentration at the cellular level, we biochemically character...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmolb.2017.00088/full |
| _version_ | 1818484285443670016 |
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| author | Giulia Murtas Silvia Sacchi Silvia Sacchi Mattia Valentino Mattia Valentino Loredano Pollegioni Loredano Pollegioni |
| author_facet | Giulia Murtas Silvia Sacchi Silvia Sacchi Mattia Valentino Mattia Valentino Loredano Pollegioni Loredano Pollegioni |
| author_sort | Giulia Murtas |
| collection | DOAJ |
| description | D-amino acid oxidase catalyzes the oxidative deamination of D-amino acids. In the brain, the NMDA receptor coagonist D-serine has been proposed as its physiological substrate. In order to shed light on the mechanisms regulating D-serine concentration at the cellular level, we biochemically characterized human DAAO (hDAAO) in greater depth. In addition to clarify the physical-chemical properties of the enzyme, we demonstrated that divalent ions and nucleotides do not affect flavoenzyme function. Moreover, the definition of hDAAO substrate specificity demonstrated that D-cysteine is the best substrate, which made it possible to propose it as a putative physiological substrate in selected tissues. Indeed, the flavoenzyme shows a preference for hydrophobic amino acids, some of which are molecules relevant in neurotransmission, i.e., D-kynurenine, D-DOPA, and D-tryptophan. hDAAO shows a very low affinity for the flavin cofactor. The apoprotein form exists in solution in equilibrium between two alternative conformations: the one at higher affinity for FAD is favored in the presence of an active site ligand. This may represent a mechanism to finely modulate hDAAO activity by substrate/inhibitor presence. Taken together, the peculiar properties of hDAAO seem to have evolved in order to use this flavoenzyme in different tissues to meet different physiological needs related to D-amino acids. |
| first_indexed | 2024-12-10T15:53:12Z |
| format | Article |
| id | doaj.art-444f8da4ca8a41df9b2d26289a29eaa7 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-10T15:53:12Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-444f8da4ca8a41df9b2d26289a29eaa72022-12-22T01:42:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2017-12-01410.3389/fmolb.2017.00088312393Biochemical Properties of Human D-Amino Acid OxidaseGiulia Murtas0Silvia Sacchi1Silvia Sacchi2Mattia Valentino3Mattia Valentino4Loredano Pollegioni5Loredano Pollegioni6Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Varese, ItalyDipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Varese, ItalyThe Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria, Milan, ItalyThe Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria, Milan, ItalySezione Adolfo Quilico, Istituto di Chimica del Riconoscimento Molecolare, CNR, Milan, ItalyDipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Varese, ItalyThe Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria, Milan, ItalyD-amino acid oxidase catalyzes the oxidative deamination of D-amino acids. In the brain, the NMDA receptor coagonist D-serine has been proposed as its physiological substrate. In order to shed light on the mechanisms regulating D-serine concentration at the cellular level, we biochemically characterized human DAAO (hDAAO) in greater depth. In addition to clarify the physical-chemical properties of the enzyme, we demonstrated that divalent ions and nucleotides do not affect flavoenzyme function. Moreover, the definition of hDAAO substrate specificity demonstrated that D-cysteine is the best substrate, which made it possible to propose it as a putative physiological substrate in selected tissues. Indeed, the flavoenzyme shows a preference for hydrophobic amino acids, some of which are molecules relevant in neurotransmission, i.e., D-kynurenine, D-DOPA, and D-tryptophan. hDAAO shows a very low affinity for the flavin cofactor. The apoprotein form exists in solution in equilibrium between two alternative conformations: the one at higher affinity for FAD is favored in the presence of an active site ligand. This may represent a mechanism to finely modulate hDAAO activity by substrate/inhibitor presence. Taken together, the peculiar properties of hDAAO seem to have evolved in order to use this flavoenzyme in different tissues to meet different physiological needs related to D-amino acids.http://journal.frontiersin.org/article/10.3389/fmolb.2017.00088/fullD-serineD-amino acid oxidaseD-cysteinesubstrate specificitystructure-function relationships |
| spellingShingle | Giulia Murtas Silvia Sacchi Silvia Sacchi Mattia Valentino Mattia Valentino Loredano Pollegioni Loredano Pollegioni Biochemical Properties of Human D-Amino Acid Oxidase Frontiers in Molecular Biosciences D-serine D-amino acid oxidase D-cysteine substrate specificity structure-function relationships |
| title | Biochemical Properties of Human D-Amino Acid Oxidase |
| title_full | Biochemical Properties of Human D-Amino Acid Oxidase |
| title_fullStr | Biochemical Properties of Human D-Amino Acid Oxidase |
| title_full_unstemmed | Biochemical Properties of Human D-Amino Acid Oxidase |
| title_short | Biochemical Properties of Human D-Amino Acid Oxidase |
| title_sort | biochemical properties of human d amino acid oxidase |
| topic | D-serine D-amino acid oxidase D-cysteine substrate specificity structure-function relationships |
| url | http://journal.frontiersin.org/article/10.3389/fmolb.2017.00088/full |
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