Structure and kinetic properties of human d-aspartate oxidase, the enzyme-controlling d-aspartate levels in brain.
Animals
Antipsychotic Agents
/ pharmacology
Binding Sites
Brain
/ metabolism
Cattle
Crystallography, X-Ray
D-Aspartate Oxidase
/ chemistry
D-Aspartic Acid
/ analysis
Dimerization
Drug Design
Humans
Kinetics
Ligands
Mice
Molecular Docking Simulation
Mutagenesis, Site-Directed
Protein Binding
Receptors, N-Methyl-D-Aspartate
/ metabolism
Substrate Specificity
Swine
NMDA receptor
d‐aspartate
d‐aspartate oxidase
flavoprotein
structure‐function relationships
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
09
07
2019
revised:
05
11
2019
accepted:
10
11
2019
entrez:
10
1
2020
pubmed:
10
1
2020
medline:
21
7
2020
Statut:
ppublish
Résumé
d-Amino acids are the "wrong" enantiomers of amino acids as they are not used in proteins synthesis but evolved in selected functions. On this side, d-aspartate (d-Asp) plays several significant roles in mammals, especially as an agonist of N-methyl-d-aspartate receptors (NMDAR), and is involved in relevant diseases, such as schizophrenia and Alzheimer's disease. In vivo modulation of d-Asp levels represents an intriguing task to cope with such pathological states. As little is known about d-Asp synthesis, the only option for modulating the levels is via degradation, which is due to the flavoenzyme d-aspartate oxidase (DASPO). Here we present the first three-dimensional structure of a DASPO enzyme (from human) which belongs to the d-amino acid oxidase family. Notably, human DASPO differs from human d-amino acid oxidase (attributed to d-serine degradation, the main coagonist of NMDAR) showing peculiar structural features (a specific active site charge distribution), oligomeric state and kinetic mechanism, and a higher FAD affinity and activity. These results provide useful insights into the structure-function relationships of human DASPO: modulating its activity represents now a feasible novel therapeutic target.
Identifiants
pubmed: 31914658
doi: 10.1096/fj.201901703R
doi:
Substances chimiques
Antipsychotic Agents
0
Ligands
0
Receptors, N-Methyl-D-Aspartate
0
D-Aspartic Acid
4SR0Q8YD1X
D-Aspartate Oxidase
EC 1.4.3.1
DDO protein, human
EC 1.4.3.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1182-1197Informations de copyright
© 2019 Federation of American Societies for Experimental Biology.
Références
Errico F, Napolitano F, Nisticò R, Centonze D, Usiello A. D‐aspartate: an atypical amino acid with neuromodulatory activity in mammals. Rev Neurosci. 2009;20:429‐440.
Sasabe J, Suzuki M. Emerging role of D‐amino acid metabolism in the innate defense. Front Microbiol. 2018;9:933.
Aliashkevich A, Alvarez L, Cava F. New insights into the mechanisms and biological roles of D‐amino acids in complex eco‐systems. Front Microbiol. 2018;9:683.
Katane M, Homma H. D‐aspartate oxidase: the sole catabolic enzyme acting on free D‐aspartate in mammals. Chem Biodivers. 2010;7:1435‐1449.
Ota N, Shi T, Sweedler JV. D‐aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids. 2012;43:1873‐1886.
Guercio GD, Panizzutti R. Potential and challenges for the clinical use of D‐serine as a cognitive enhancer. Front Psychiatry. 2018;9:14.
Pollegioni L, Sacchi S. Metabolism of the neuromodulator D‐serine. Cell Mol Life Sci. 2010;67:2387‐2404.
Wolosker H. Serine racemase and the serine shuttle between neurons and astrocytes. Biochim Biophys Acta. 2011;1814:1558‐1566.
Wolosker H, D'Aniello A, Snyder SH. D‐aspartate disposition in neuronal and endocrine tissues: ontogeny, biosynthesis and release. Neuroscience. 2000;100:183‐189.
Di Fiore MM, Santillo A, Chieffi Baccari G. Current knowledge of D‐aspartate in glandular tissues. Amino Acids. 2014;46:1805‐1818.
Schell MJ, Cooper OB, Snyder SH. D‐aspartate localizations imply neuronal and neuroendocrine roles. Proc Natl Acad Sci USA. 1997;94:2013‐2018.
Errico F, Napolitano F, Nisticò R, Usiello A. New insights on the role of free D‐aspartate in the mammalian brain. Amino Acids. 2012;43:1861‐1871.
Hashimoto A, Kumashiro S, Nishikawa T, et al. Embryonic development and postnatal changes in free D‐aspartate and D‐serine in the human prefrontal cortex. J. Neurochem. 1993;61:348‐351.
Errico F, Nisticò R, Napolitano F, et al. Increased D‐aspartate brain content rescues hippocampal age‐related synaptic plasticity deterioration of mice. Neurobiol Aging. 2011;32:2229‐2243.
Ito T, Hayashida M, Kobayashi S, et al. Serine racemase is involved in D‐aspartate biosynthesis. J Biochem. 2016;160:345‐353.
Zaar K, Köst HP, Schad A, Völkl A, Baumgart E, Fahimi HD. Cellular and subcellular distribution of D‐aspartate oxidase in human and rat brain. J Comp Neurol. 2002;450:272‐282.
D'Aniello S, Somorjai I, Garcia‐Fernàndez J, Topo E, D'Aniello A. D‐aspartic acid is a novel endogenous neurotransmitter. FASEB J. 2011;25:1014‐1027.
Molinaro G, Pietracupa S, Di Menna L, et al. D‐aspartate activates mGlu receptors coupled to polyphosphoinositide hydrolysis in neonate rat brain slices. Neurosci Lett. 2010;478:128‐130.
Cristino L, Luongo L, Squillace M, et al. D‐aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. Neurobiol Aging. 2015;36:1890‐1902.
Errico F, Napolitano F, Squillace M, et al. Decreased levels of D‐aspartate and NMDA in the prefrontal cortex and striatum of patients with schizophrenia. J Psychiatr Res. 2013;47:1432‐1437.
Errico F, Nisticò R, Palma G, et al. Increased levels of D‐aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci. 2008;37:236‐246.
D'Aniello A, Luongo L, Romano R, et al. D‐aspartic acid ameliorates painful and neuropsychiatric changes and reduces β‐amyloid Aβ. Neurosci Lett. 2017;651:151‐158.
De Rosa V, Secondo A, Pannaccione A, et al. D‐aspartate treatment attenuates myelin damage and stimulates myelin repair. EMBO Mol Med. 2019;11(1):pii:e9278.
Setoyama C, Miura R. Structural and functional characterization of the human brain D‐aspartate oxidase. J Biochem. 1997;121:798‐803.
Katane M, Kawata T, Nakayama K, et al. Characterization of the enzymatic and structural properties of human D‐aspartate oxidase and comparison with those of the rat and mouse enzymes. Biol Pharm Bull. 2015;38:298‐305.
Katane M, Kuwabara H, Nakayama K, et al. Rat D‐aspartate oxidase is more similar to the human enzyme than the mouse enzyme. Biochim Biophys Acta Proteins Proteom. 2018;1866:806‐812.
Katane M, Yamada S, Kawaguchi G, et al. Identification of novel D‐aspartate oxidase inhibitors by in silico screening and their functional and structural characterization in vitro. J Med Chem. 2015;58:7328‐7340.
Katane M, Kanazawa R, Kobayashi R, et al. Structure‐function relationships in human D‐aspartate oxidase: characterisation of variants corresponding to known single nucleotide polymorphisms. Biochim Biophys Acta Proteins Proteom. 2017;1865:1129‐1140.
Hefti MH, Vervoort J, van Berkel WJ. (2003) Deflavination and reconstitution of flavoproteins. Eur J Biochem. 2003;270:4227‐4242.
Molla G, Sacchi S, Bernasconi M, Pilone MS, Fukui K, Pollegioni L. Characterization of human D‐amino acid oxidase. FEBS Lett. 2006;580:2358‐2364.
Caldinelli L, Molla G, Sacchi S, Pilone MS, Pollegioni L. Relevance of weak flavin binding in human D‐amino acid oxidase. Protein Sci. 2009;18:801‐810.
Gibson QH, Swoboda BE, Massey V. Kinetics and mechanism of action of glucose oxidase. J Biol Chem. 1964;239:3927‐3934.
Senda M, Yamamoto A, Tanaka H, Ishida T, Horiike K, Senda T. Crystallization and preliminary crystallographic analysis of D‐aspartate oxidase from porcine kidney. Acta Crystallogr. Sect F Struct Biol Cryst Commun. 2012;68:644‐646.
Kabsch W. XDS. Acta Crystallogr D Biol Crystallogr. 2010;66:125‐132.
Tickle IJ. (2010) STARANISO. Cambridge, UK: Global Phasing Ltd.; 2018.
Emsley P, Cowtan K. Coot: model‐building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004;60:2126‐2132.
Adams PD, Afonine PV, Bunkóczi G, et al. PHENIX: a comprehensive Python‐based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010;66:213‐221.
Chen VB, Arendall WB, Headd JJ, et al. MolProbity: all‐atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2010;66:12‐21.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455‐461.
Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4:17.
Negri A, Massey V, Williams CH. D‐aspartate oxidase from beef kidney. Purification and properties. J Biol Chem. 1987;262:10026‐10034.
Katane M, Hanai T, Furuchi T, Sekine M, Homma H. Hyperactive mutants of mouse D‐aspartate oxidase: mutagenesis of the active site residue serine 308. Amino Acids. 2008;35:75‐82.
Takahashi S, Takahashi T, Kera Y, Matsunaga R, Shibuya H, Yamada RH. Cloning and expression in Escherichia coli of the D‐aspartate oxidase gene from the yeast Cryptococcus humicola and characterization of the recombinant enzyme. J Biochem. 2004;135:533‐540.
Pawelek PD, Cheah J, Coulombe R, Macheroux P, Ghisla S, Vrielink A. The structure of L‐amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site. EMBO J. 2000;19:4204‐4215.
Pollegioni L, Molla G, Campaner S, Martegani E, Pilone MS. Cloning, sequencing and expression in E coli of a D‐amino acid oxidase cDNA from Rhodotorula gracilis active on cephalosporin C. J Biotechnol. 1997;58:115‐123.
Massey V, Hemmerich P. Active‐site probes of flavoproteins. Biochem Soc Trans. 1980;8:246‐257.
Fraaije MW, Mattevi A. Flavoenzymes: diverse catalysts with recurrent features. Trends Biochem Sci. 2000;25:126‐132.
Holm L, Rosenström P. Dali server: conservation mapping in 3D. Nucleic Acids Res. 2010;38:W545‐W549.
Mattevi A, Vanoni MA, Todone F, et al. Crystal structure of D‐amino acid oxidase: a case of active site mirror‐image convergent evolution with flavocytochrome b2. Proc Natl Acad Sci USA. 1996;93:7496‐7501.
Umhau S, Pollegioni L, Molla G, et al. The x‐ray structure of D‐amino acid oxidase at very high resolution identifies the chemical mechanism of flavin‐dependent substrate dehydrogenation. Proc Natl Acad Sci USA. 2000;97:12463‐12468.
Pollegioni L, Diederichs K, Molla G, et al. Yeast D‐amino acid oxidase: structural basis of its catalytic properties. J Mol Biol. 2002;324:535‐546.
Mörtl M, Diederichs K, Welte W, et al. Structure‐function correlation in glycine oxidase from Bacillus subtilis. J Biol Chem. 2004;279:29718‐29727.
Kawazoe T, Tsuge H, Pilone MS, Fukui K. Crystal structure of human D‐amino acid oxidase: context‐dependent variability of the backbone conformation of the VAAGL hydrophobic stretch located at the si‐face of the flavin ring. Protein Sci. 2006;15:2708‐2717.
Dym O, Eisenbergs D. Sequence‐structure analysis of FAD‐containing proteins. Protein Sci. 2001;10:1712‐1728.
Caldinelli L, Molla G, Bracci L, et al. Effect of ligand binding on human D‐amino acid oxidase: implications for the development of new drugs for schizophrenia treatment. Protein Sci. 2010;19:1500‐1512.
Negri A, Massey V, Williams CH, Schopfer LM. The kinetic mechanism of beef kidney D‐aspartate oxidase. J Biol Chem. 1988;263:13557‐13563.
Decker LE, Byerrum RU. The relationship between dietary riboflavin concentration and the tissue concentration of riboflavin‐containing coenzymes and enzymes. J Nutr. 1954;53:303‐315.
Pollegioni L, Piubelli L, Sacchi S, Pilone MS, Molla G. Physiological functions of D‐amino acid oxidases: from yeast to humans. Cell Mol Life Sci. 2007;64:1373‐1394.
Sacchi S, Rosini E, Pollegioni L, Molla G. D‐amino acid oxidase inhibitors as a novel class of drugs for schizophrenia therapy. Curr Pharm Des. 2013;19:2499‐2511.
Ferraris D, Duvall B, Ko YS, et al. Synthesis and biological evaluation of D‐amino acid oxidase inhibitors. J Med Chem. 2008;51:3357‐3359.
Pollegioni L, Langkau B, Tischer W, Ghisla S, Pilone MS. Kinetic mechanism of D‐amino acid oxidases from Rhodotorula gracilis and Trigonopsis variabilis. J Biol Chem. 1993;268:13850‐13857.
Dalziel K. The interpretation of kinetic data for enzyme‐catalysed reactions involving three substrates. Biochem J. 1969;114:547‐556.
Strickland S, Palmer G, Massey V. Determination of dissociation constants and specific rate constants of enzyme‐substrate (or protein‐ligand) interactions from rapid reaction kinetic data. J Biol Chem. 1975;250:4048‐4052.
Weil ZM, Huang AS, Beigneux A, et al. Behavioural alterations in male mice lacking the gene for D‐aspartate oxidase. Behav Brain Res. 2006;171:295‐302.
Palazzo E, Luongo L, Guida F, et al. D‐aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice. Amino Acids. 2016;48:1553‐1567.
Frattini LF, Piubelli L, Sacchi S, Molla G, Pollegioni L. Is rat an appropriate animal model to study the involvement of D‐serine catabolism in schizophrenia? Insights from characterization of D‐amino acid oxidase. FEBS J. 2011;278:4362‐4373.
Sacchi S, Cappelletti P, Giovannardi S, Pollegioni L. Evidence for the interaction of D‐amino acid oxidase with pLG72 in a glial cell line. Mol Cell Neurosci. 2011;48:20‐28.
Sacchi S, Binelli G, Pollegioni L. G72 primate‐specific gene: a still enigmatic element in psychiatric disorders. Cell Mol Life Sci. 2016;73:2029‐2039.
Van Veldhoven PP, Brees C, Mannaerts GP. D‐aspartate oxidase, a peroxisomal enzyme in liver of rat and man. Biochim. Biophys. Acta. 1991;1073:203‐208.