{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:10:44Z","timestamp":1792782644145,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T00:00:00Z","timestamp":1275436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Fondo di Ateneo per la Ricerca, Fondazione CARIPLO","id":[{"id":"https:\/\/ror.org\/01gb56c55","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In human brain the flavoprotein\n                    <jats:sc>D<\/jats:sc>\n                    \u2010amino acid oxidase (hDAAO) is responsible for the degradation of the neuromodulator\n                    <jats:sc>D<\/jats:sc>\n                    \u2010serine, an important effector of NMDA\u2010receptor mediated neurotransmission. Experimental evidence supports the concept that\n                    <jats:sc>D<\/jats:sc>\n                    \u2010serine concentration increase by hDAAO inhibition may represent a valuable therapeutic approach to improve the symptoms in schizophrenia patients. This study investigated the effects on hDAAO conformation and stability of the substrate\n                    <jats:sc>D<\/jats:sc>\n                    \u2010serine (or of the pseudo\u2010substrate trifluoro\u2010\n                    <jats:sc>D<\/jats:sc>\n                    \u2010alanine), the FAD cofactor, and two inhibitors (benzoate, a classical substrate\u2010competitive inhibitor and the drug chlorpromazine (CPZ), which competes with the cofactor). We demonstrated that all these compounds do not alter the interaction of hDAAO with its physiological partner pLG72. The ligands used affect the tertiary structure of hDAAO differently: benzoate or trifluoro\u2010\n                    <jats:sc>D<\/jats:sc>\n                    \u2010alanine binding increases the amount of the holoenzyme form in solution and stabilizes the flavoprotein, while CPZ binding favors a protein conformation resembling that of the apoprotein, which is more sensitive to degradation. Interestingly, the apoprotein form of hDAAO binds the substrate\n                    <jats:sc>D<\/jats:sc>\n                    \u2010serine: this interaction increases FAD binding thus increasing the amount of active holoenzyme in solution. Benzoate and CPZ similarly modify the short\u2010term cellular\n                    <jats:sc>D<\/jats:sc>\n                    \u2010serine concentration but affect the cellular concentration of hDAAO differently. In conclusion, the different alteration of hDAAO conformation and stability by the ligands used represents a further parameter to take into consideration during the development of new drugs to cope schizophrenia.\n                  <\/jats:p>","DOI":"10.1002\/pro.429","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T16:59:57Z","timestamp":1275497997000},"page":"1500-1512","source":"Crossref","is-referenced-by-count":55,"title":["Effect of ligand binding on human\n                    <scp>D<\/scp>\n                    \u2010amino acid oxidase: Implications for the development of new drugs for schizophrenia treatment"],"prefix":"10.1002","volume":"19","author":[{"given":"Laura","family":"Caldinelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Molla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Lelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pileri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Cappelletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredano","family":"Pollegioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6558-4"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.01.071"},{"key":"e_1_2_6_4_2","article-title":"Metabolism 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