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dc.contributor.author Ambrus, Attila
dc.contributor.author Wang Junjie
dc.contributor.author Mizsei, Réka
dc.contributor.author Zámbó, Zsófia
dc.contributor.author Törőcsik, Beáta
dc.contributor.author Jordan Frank
dc.contributor.author Ádám-Vizi, Veronika
dc.date.accessioned 2021-02-05T13:31:51Z
dc.date.available 2021-02-05T13:31:51Z
dc.date.issued 2016
dc.identifier 84983749039
dc.identifier.citation journalVolume=1862;journalIssueNumber=11;journalTitle=BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE;pagerange=2098-2109;journalAbbreviatedTitle=BBA-MOL BASIS DIS;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/8480
dc.identifier.uri doi:10.1016/j.bbadis.2016.08.013
dc.description.abstract Pathogenic amino acid substitutions of the common E3 component (hE3) of the human alpha-ketoglutarate dehydrogenase and the pyruvate dehydrogenase complexes lead to severe metabolic diseases (E3 deficiency), which usually manifest themselves in cardiological and/or neurological symptoms and often cause premature death. To date, 14 disease-causing amino acid substitutions of the hE3 component have been reported in the clinical literature. None of the pathogenic protein variants has lent itself to high-resolution structure elucidation by X-ray or NMR. Hence, the structural alterations of the hE3 protein caused by the disease-causing mutations and leading to dysfunction, including the enhanced generation of reactive oxygen species by selected disease-causing variants, could only be speculated. Here we report results of an examination of the effects on the protein structure of ten pathogenic mutations of hE3 using hydrogen/deuterium-exchange mass spectrometry (HDX-MS), a new and state-of-the-art approach of solution structure elucidation. On the basis of the results, putative structural and mechanistic conclusions were drawn regarding the molecular pathogenesis of each disease-causing hE3 mutation addressed in this study. © 2016 Elsevier B.V.
dc.format.extent 2098-2109
dc.title Structural alterations induced by ten disease-causing mutations of human dihydrolipoamide dehydrogenase analyzed by hydrogen/deuterium-exchange mass spectrometry: Implications for the structural basis of E3 deficiency
dc.type Journal Article
dc.date.updated 2020-09-22T08:57:23Z
dc.language.rfc3066 en
dc.rights.holder Elsevier
dc.identifier.mtmt 3114546
dc.identifier.wos 000384860200008
dc.identifier.pubmed 27544700
dc.contributor.department Orvosi Biokémiai Intézet
dc.contributor.department MTA-SE Neurobiokémiai Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Attila Ambrus, Junjie Wang and Reka Mizsei contributed equally to this work. Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, Budapest, Hungary Department of Chemistry, Rutgers University, Newark, NJ, United States Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, United States Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Cited By :9 Export Date: 28 May 2020 CODEN: BBADE Correspondence Address: Ambrus, A.; Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis UniversityHungary; email: ambrus.attila@med.semmelweis-univ.hu Chemicals/CAS: amino acid, 65072-01-7; deuterium, 7782-39-0; dihydrolipoamide dehydrogenase, 37340-89-9, 9001-18-7; hydrogen, 12385-13-6, 1333-74-0 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Hungarian Scientific Research Fund, OTKA, 112230 Funding details: Magyar Tudományos Akadémia, MTA, 02001 Funding text 1: We are grateful to Drs. Oliver Ozohanics, Karoly Vekey (both from the Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary) and Arpad Somogyi (Ohio State University, Columbus, OH, USA) for their contributions to the method development in mass spectrometry. Financial support is gratefully acknowledged from the Hungarian Academy of Sciences (MTA grant 02001 to V.A.-V.), the Hungarian Scientific Research Fund (OTKA, grant 112230 to V.A.-V.), the Hungarian Brain Research Program (grant KTIA_13_NAP-A-III/6 to V.A.-V.), the Bolyai and the Fulbright Fellowships (to A.A.), NIH - R15GM116077 and NSF-CHE - 1402675 (to F.J.).


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