{"created":"2023-06-26T11:01:06.022212+00:00","id":1717,"links":{},"metadata":{"_buckets":{"deposit":"79fa98fc-95a9-4ab6-8af7-59a6876951ea"},"_deposit":{"created_by":29,"id":"1717","owners":[29],"pid":{"revision_id":0,"type":"depid","value":"1717"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00001717","sets":["6:74"]},"author_link":["10322","10324","10321","10323","10325","10326"],"item_10001_biblio_info_7":{"attribute_name":"Bibliographic Information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-01-15","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"108263","bibliographicVolumeNumber":"682","bibliographic_titles":[{},{"bibliographic_title":"Archives of Biochemistry and Biophysics","bibliographic_titleLang":"en"}]}]},"item_10001_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Montioli, Riccardo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Bisello, Giovanni"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Dindo, Mirco"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Rossignoli, Giada"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Voltattorni, Carla Borri"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Bertoldi, Mariarita"}],"nameIdentifiers":[{}]}]},"item_10001_description_5":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"AADC deficiency is a rare genetic disease caused by mutations in the gene of aromatic amino acid decarboxylase, the pyridoxal 5'-phosphate dependent enzyme responsible for the synthesis of dopamine and serotonin. Here, following a biochemical approach together with an in silico bioinformatic analysis, we present a structural and functional characterization of 13 new variants of AADC. The amino acid substitutions are spread over the entire protein from the N-terminal (V60A), to its loop1 (H70Y and F77L), to the large domain (G96R) and its various motifs, i.e. loop2 (A110E), or a core beta-barrel either on the surface (P210L, F251S and E283A) or in a more hydrophobic milieu (L222P, F237S and W267R) or loop3 (L353P), and to the C-terminal domain (R453C). Results show that the beta-barrel variants exhibit a low solubility and those belonging to the surface tend to aggregate in their apo form, leading to the identification of a new enzymatic phenotype for AADC deficiency. Moreover, five variants of residues belonging to the large interface of AADC (V60A, G96R, A110E, L353P and R453C) are characterized by a decreased catalytic efficiency. The remaining ones (H70Y and F77L) present features typical of apo-to-holo impaired transition. Thus, defects in catalysis or in the acquirement of the correct holo structure are due not only to specific local domain effects but also to long-range effects at either the protein surface or the subunit interface. Altogether, the new characterized enzymatic phenotypes represent a further step in the elucidation of the molecular basis for the disease.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_10001_relation_13":{"attribute_name":"PubMedNo.","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:pmid/31953134","subitem_relation_type_select":"PMID"}}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1016/j.abb.2020.108263","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_17":{"attribute_name":"Related site","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.sciencedirect.com/science/article/pii/S0003986119310586","subitem_relation_type_select":"URI"}}]},"item_10001_rights_15":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_rights":"This article/chapter was published in Journal of Archives of Biochemistry and Biophysics, Volume 682, Riccardo Montioli, Giovanni Bisello, Mirco Dindo, Giada Rossignoli, Carla Borri Voltattorni, Mariarita Bertoldi, New variants of AADC deficiency expand the knowledge of enzymatic phenotypes, 108263, © Elsevier 2020."}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0003-9861","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"1096-0384","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"Author's flag","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-01-15"}],"displaytype":"detail","filename":"Paper_Dindo.pdf","filesize":[{"value":"426.3 kB"}],"format":"application/pdf","license_note":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International(https://creativecommons.org/licenses/by-nc-nd/4.0/)","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Paper_Dindo","url":"https://oist.repo.nii.ac.jp/record/1717/files/Paper_Dindo.pdf"},"version_id":"41488ead-5ff8-4804-bfda-3e533a4d81a6"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"PLP","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"pyridoxal 5′-phosphate","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"AADC","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"aromatic amino acid decarboxylase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Dopa","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"3,4-dihydroxyphenylalanine","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"New variants of AADC deficiency expand the knowledge of enzymatic phenotypes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"New variants of AADC deficiency expand the knowledge of enzymatic phenotypes","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"29","path":["74"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-10-09"},"publish_date":"2020-10-09","publish_status":"0","recid":"1717","relation_version_is_last":true,"title":["New variants of AADC deficiency expand the knowledge of enzymatic phenotypes"],"weko_creator_id":"29","weko_shared_id":29},"updated":"2023-06-26T11:44:11.887762+00:00"}