https://m2.mtmt.hu/ eng 2026-09-22 11:36 JournalArticle 30799456 APPROVED true 0 false 2026-06-17T10:37:54.931+0000 2022-12-22T15:22:45.486+0000 2019-09-12T12:59:48.664+0000 true 10054198 xBökönyi Zita /api/admin/10054198 Admin Zita xBökönyi (INAKTÍV_SE_AOK_OBI_Admin5_BZ, admin) true 10054198 2026-04-21T08:48:43.325+0000 2019-12-09T07:43:29.854+0000 true 10026589 Tichy Rita /api/admin/10026589 Admin Rita Tichy (SE_KK_Admin5_TR, admin) true 10026589 Admin 10065569 /api/admin/10065569 Éva Pécsi (MTMT Közp 2,3, admin) Pécsi Éva true true 2021-06-29T17:12:08.186+0000 true false true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Article (Journal Article) 101 true 10000059 true 1 /api/category/1 Category Scientific true 1 Szabo, Eszter true true /api/journal/1807 REVIEWED HUMAN MOLECULAR GENETICS 0964-6906 1460-2083 true false 1807 false 1807 true 0964-6906 1460-2083 Journal FOREIGN 28 20 3339 3354 3339 16 2019 Human dihydrolipoamide dehydrogenase (hLADH, hE3) deficiency (OMIM# 246900) is an often prematurely lethal genetic disease usually caused by inactive or partially inactive hE3 variants. Here we report the crystal structure of wild-type hE3 at an unprecedented high resolution of 1.75 Å and the structures of six disease-causing hE3 variants at resolutions ranging from 1.44 to 2.34 Å. P453L proved to be the most deleterious substitution in structure as aberrations extensively compromised the active site. The most prevalent G194C-hE3 variant primarily exhibited structural alterations close to the substitution site, whereas the nearby cofactor-binding residues were left unperturbed. The G426E substitution mainly interfered with the local charge distribution introducing dynamics to the substitution site in the dimer interface; G194C and G426E both led to minor structural changes. The R460G, R447G, and I445M substitutions all perturbed a solvent accessible channel, the so-called H+/H2O channel, leading to the active site. Molecular pathomechanisms of enhanced reactive oxygen species (ROS) generation and impaired binding to multienzyme complexes were also addressed according to the structural data for the relevant mutations. In summary, we present here for the first time a comprehensive study that links three-dimensional structures of disease-causing hE3 variants to residual hLADH activities, altered capacities for ROS generation, compromised affinities for multienzyme complexes, and eventually clinical symptoms. Our results may serve as useful starting points for future therapeutic intervention approaches. Funding 2000066 /api/funding/2000066 (EFOP-3.6.3-VEKOP-16-2017-00009) false true true true 2019 true true true false true false NONE 2026-06-17 false 21 0 21 16 4 21 21 20 21 21 21 16 16 16 5 0 21 16 21 16 0 13 13 Folyóiratcikk Journal Article 24 21 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2020 0 2 1 2 1 2021 0 8 7 8 7 2022 0 3 3 3 3 2023 0 5 3 5 3 2024 0 2 1 2 1 2025 0 0 0 0 0 2026 0 1 1 1 1 D1 false 10060658,10059307,10000177 false false false 2019-12-08T07:43:29.614+0000 Biokémiai Tanszék (SE / AOK / I / BMBI); MTA-SE Neurobiokémiai Kutatócsoport (SE / AOK / I / OBI); Orvosi Biokémiai Intézet (SE / AOK / I) 7 18 3 15 0 true 10065569 Language 10002 /api/language/10002 English Angol English true 2 true PersonAuthorship 87913724 /api/authorship/87913724 Szabo, Eszter [Szabó, Eszter (biokémia), author] Department of Medical Biochemistry (SU / FM / I) 1 0.06666667 true false false Author 10060658 /api/author/10060658 Eszter Szabó (biokémia) Szabó Eszter true 10060658 true Szabo Eszter true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913725 /api/authorship/87913725 Wilk, Piotr 2 0.06666667 false false false Wilk Piotr true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913726 /api/authorship/87913726 Nagy, Balint [Csuka Nagy, Bálint (szerkezeti biokémia), author] Department of Medical Biochemistry (SU / FM / I) 3 0.06666667 false false false Author 10059307 /api/author/10059307 Bálint Csuka Nagy (szerkezeti biokémia) Csuka Nagy Bálint true 10059307 true Nagy Balint true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913727 /api/authorship/87913727 Zambo, Zsofia [Zámbó, Zsófia Melinda (biokémia), author] Department of Medical Biochemistry (SU / FM / I) 4 0.06666667 false false false Author 10060538 /api/author/10060538 Zsófia Melinda Zámbó (biokémia) Zámbó Zsófia Melinda true 10060538 true Zambo Zsofia true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913728 /api/authorship/87913728 Bui, David [Bui, Dávid (biokémia és molek...), author] Biokémiai Tanszék (SU / FM / I / BMBI) 5 0.06666667 false false false Author 10080521 /api/author/10080521 Dávid Bui (biokémia és molekuláris biológia) Bui Dávid true true Bui David true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913729 /api/authorship/87913729 Weichsel, Andrzej 6 0.06666667 false false false Weichsel Andrzej true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913730 /api/authorship/87913730 Arjunan, Palaniappa 7 0.06666667 false false false Arjunan Palaniappa true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913731 /api/authorship/87913731 Torocsik, Beata [Törőcsik, Beáta (orvosi biokémia), author] Department of Medical Biochemistry (SU / FM / I) 8 0.06666667 false false false Author 10003430 /api/author/10003430 Beáta Törőcsik (orvosi biokémia) Törőcsik Beáta true 10003430 true Torocsik Beata true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913732 /api/authorship/87913732 Hubert, Agnes 9 0.06666667 false false false Hubert Agnes true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913733 /api/authorship/87913733 Furey, William 10 0.06666667 false false false Furey William true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913734 /api/authorship/87913734 Montfort, William R 11 0.06666667 false false false Montfort William R true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913735 /api/authorship/87913735 Jordan, Frank 12 0.06666667 false false false Jordan Frank true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913736 /api/authorship/87913736 Weiss, Manfred S 13 0.06666667 false false false Weiss Manfred S true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913737 /api/authorship/87913737 Adam-Vizi, Vera [Ádám, Veronika (idegtudomány, bio...), author] Department of Medical Biochemistry (SU / FM / I); MTA-SE Research Group Neuro biochemical (SU / FM / I / DMB) 14 0.06666667 false false false Author 10000397 /api/author/10000397 Veronika Ádám (idegtudomány, biokémia) Ádám Veronika true 10000397 true Adam-Vizi Vera true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 87913738 /api/authorship/87913738 Ambrus, Attila ✉ [Ambrus, Attila (Biokémia), author] Department of Medical Biochemistry (SU / FM / I); MTA-SE Research Group Neuro biochemical (SU / FM / I / DMB) 15 0.06666667 false true true Author 10000177 /api/author/10000177 Attila Ambrus (Biokémia) Ambrus Attila true 10000177 true Ambrus Attila true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PublicationIdentifier 15890796 /api/publicationidentifier/15890796 DOI: 10.1093/hmg/ddz177 PlainSource 6 /api/publicationsource/6 DOI PublicationSourceType 10001 /api/publicationsourcetype/10001 DOI true true true DOI DOI https://doi.org/@@@ true true 6 true IDENTICAL 10.1093/hmg/ddz177 https://doi.org/10.1093/hmg/ddz177 false true PublicationIdentifier 16837006 /api/publicationidentifier/16837006 WoS: 000506805800001 PlainSource 1 /api/publicationsource/1 WoS PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 000506805800001 https://www.webofscience.com/wos/woscc/full-record/000506805800001 true true PublicationIdentifier 16545566 /api/publicationidentifier/16545566 Scopus: 85076197586 PlainSource 3 /api/publicationsource/3 Scopus PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 85076197586 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85076197586 true true PublicationIdentifier 15890795 /api/publicationidentifier/15890795 PubMed: 31334547 PlainSource 17 /api/publicationsource/17 PubMed PublicationSourceType 10003 /api/publicationsourcetype/10003 Indexelő adatbázis false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 31334547 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31334547&dopt=Abstract false true PublicationIdentifier 31302039 /api/publicationidentifier/31302039 Other URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076197586&doi=10.1093%2Fhmg%2Fddz177&partnerID=40&md5=57a49529a85b3264e902e9df7626df39 PlainSource 40 /api/publicationsource/40 Other URL PublicationSourceType 10006 /api/publicationsourcetype/10006 Link true true true Egyéb URL Other URL @@@ true true 40 true NONE IDENTICAL https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076197586&doi=10.1093%2Fhmg%2Fddz177&partnerID=40&md5=57a49529a85b3264e902e9df7626df39 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076197586&doi=10.1093%2Fhmg%2Fddz177&partnerID=40&md5=57a49529a85b3264e902e9df7626df39 false true PublicationIdentifier 31866743 /api/publicationidentifier/31866743 Other URL: https://www.scopus.com/pages/publications/85076197586?origin=resultslist PlainSource 40 /api/publicationsource/40 Other URL PublicationSourceType 10006 /api/publicationsourcetype/10006 Link true true true Egyéb URL Other URL @@@ true true 40 true NONE IDENTICAL https://www.scopus.com/pages/publications/85076197586?origin=resultslist https://www.scopus.com/pages/publications/85076197586?origin=resultslist false true Classification 10575 /api/classification/10575 Biochemistry and molecular biology true true Classification 10545 /api/classification/10545 Biological sciences true true SjrRating 10807185 /api/sjrrating/10807185 sjr:D1 (2019) Scopus - Genetics (clinical) HUMAN MOLECULAR GENETICS 0964-6906 1460-2083 9 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr sjr true true ClassificationExternal 2716 /api/classificationexternal/2716 Scopus - Genetics (clinical) true 2716 true D1 DIRECT true true /api/publication/30799456 Szabo Eszter et al. Underlying molecular alterations in human dihydrolipoamide dehydrogenase deficiency revealed by structural analyses of disease-causing enzyme variants. (2019) HUMAN MOLECULAR GENETICS 0964-6906 1460-2083 28 20 3339-3354<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10060658"><a href="/gui2/?type=authors&mode=browse&sel=10060658" target="_blank">Szabo Eszter (<span class="authorship-author-name">Szabó Eszter</span> <span class="authorAux-mtmt"> biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Wilk Piotr </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10059307"><a href="/gui2/?type=authors&mode=browse&sel=10059307" target="_blank">Nagy Balint (<span class="authorship-author-name">Csuka Nagy Bálint</span> <span class="authorAux-mtmt"> szerkezeti biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10060538"><a href="/gui2/?type=authors&mode=browse&sel=10060538" target="_blank">Zambo Zsofia (<span class="authorship-author-name">Zámbó Zsófia Melinda</span> <span class="authorAux-mtmt"> biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10080521"><a href="/gui2/?type=authors&mode=browse&sel=10080521" target="_blank">Bui David (<span class="authorship-author-name">Bui Dávid</span> <span class="authorAux-mtmt"> biokémia és molekuláris biológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weichsel Andrzej </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Arjunan Palaniappa </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10003430"><a href="/gui2/?type=authors&mode=browse&sel=10003430" target="_blank">Torocsik Beata (<span class="authorship-author-name">Törőcsik Beáta</span> <span class="authorAux-mtmt"> orvosi biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hubert Agnes </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Furey William </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Montfort William R </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Jordan Frank </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Weiss Manfred S </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000397"><a href="/gui2/?type=authors&mode=browse&sel=10000397" target="_blank">Adam-Vizi Vera (<span class="authorship-author-name">Ádám Veronika</span> <span class="authorAux-mtmt"> idegtudomány, biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/<span title="Department of Medical Biochemistry">DMB</span>/MTA-SE Research Group Neuro biochemical</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000177"><a href="/gui2/?type=authors&mode=browse&sel=10000177" target="_blank">Ambrus Attila ✉ (<span class="authorship-author-name">Ambrus Attila</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/Department of Medical Biochemistry; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/<span title="Department of Medical Biochemistry">DMB</span>/MTA-SE Research Group Neuro biochemical</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;30799456" target="_blank">Underlying molecular alterations in human dihydrolipoamide dehydrogenase deficiency revealed by structural analyses of disease-causing enzyme variants</a></div> <div> <span class="journal-title">HUMAN MOLECULAR GENETICS</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0964-6906">0964-6906</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1460-2083">1460-2083</a>)</span>: <span class="journal-volume">28</span> <span class="journal-issue">20</span> <span class="page"> pp 3339-3354 </span> <span class="year">(2019)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1093/hmg/ddz177" target="_blank" href="https://doi.org/10.1093/hmg/ddz177"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000506805800001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000506805800001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85076197586" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85076197586"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="31334547" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31334547&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" None "> <a style="color:blue" title="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076197586&doi=10.1093%2Fhmg%2Fddz177&partnerID=40&md5=57a49529a85b3264e902e9df7626df39" target="_blank" href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85076197586&doi=10.1093%2Fhmg%2Fddz177&partnerID=40&md5=57a49529a85b3264e902e9df7626df39"> Other URL </a> </span> <span class="id identifier oa_NONE" title=" None "> <a style="color:blue" title="https://www.scopus.com/pages/publications/85076197586?origin=resultslist" target="_blank" href="https://www.scopus.com/pages/publications/85076197586?origin=resultslist"> Other URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Genetics (clinical)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Genetics&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> <div class="journal-subject">Journal subject: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 21</span> | Independent citation: 16 | Self citation: 5 | Unknown citation: 0 | Number of citations in WoS: 20 | Number of citations in Scopus:&nbsp;21 | WoS/Scopus assigned:&nbsp;21 | Number of citations with DOI:&nbsp;21 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;30799456&sort=publishedYear,desc&sort=title"> Number of cited publications: 13 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 30799456</span> | <span class="status-data status-APPROVED"> Published </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">PubMed (pubmed_result (1).xml, 2019-09-12)</span> </div> <div class="funder"> Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009) Funder: EFOP-VEKOP </div> <div class="lastModified">Last Modified: 2022.12.22. 16:22 Andrea Vándor (VA, admin) </div> <div class="lockedBy">Centrally managed 2021.06.29. 19:12 Éva Pécsi (MTMT Közp 2,3, admin) </div> </div></div>