Structure and Mechanism of the Flavoenzyme Lipoamide Dehydrogenase from Escherichia coli

Tietzel, Michael

dc.contributor.advisor	Tittmann, Kai Prof. Dr.
dc.contributor.author	Tietzel, Michael
dc.date.accessioned	2016-08-29T09:34:16Z
dc.date.available	2016-08-29T09:34:16Z
dc.date.issued	2016-08-29
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0028-8818-7
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-5813
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Structure and Mechanism of the Flavoenzyme Lipoamide Dehydrogenase from Escherichia coli	de
dc.type	doctoralThesis	de
dc.contributor.referee	Tittmann, Kai Prof. Dr.
dc.date.examination	2015-09-10
dc.description.abstracteng	The flavoenzyme lipoamide dehydrogenase (E3) is an ubiquitously distributed enzyme which is part of several multienzyme complexes involved in cellular carbon metabolism thus contributing to cellular homeostasis. It catalyzes the regeneration of reduced lipoamide cofactors using a disulfide exchange reaction of reduced lipoamide with a redox active cystine, transfer of two reducing equivalents from this disulfide bridge to the flavin cofactor, involving a transient covalent conjugate, and hydride transfer from the flavin site to final electron acceptor NAD+. We have been using protein crystallography to gather structural snapshots of the reaction mechanism, and were determining X-ray crystallographic structures of the E.coli enzyme at different redox states: one in which the redox-active disulfide bridge is partially (~50%) reduced, and one where the disulfide is almost completely (>90%) reduced. The structural analysis permits the observation of electron density that is consistent with a flavin-C4a-cysteinyl adduct, whose existence has been predicted but has never been proven experimentally for this enzyme class. On the basis of our structural findings, we propose that the distinct E3 active site architecture is the fundament for the adduct’s transient nature and thus prevents the well-known longevity typical for flavin-C4a-cysteinyl adducts in LOV domain photoreceptors.	de
dc.contributor.coReferee	Ficner, Ralf Prof. Dr.
dc.contributor.thirdReferee	Rodnina, Marina Prof. Dr.
dc.contributor.thirdReferee	Mata, Ricardo A. Jun.-prof. Dr.
dc.contributor.thirdReferee	Commichau, Fabian Moritz Dr.
dc.subject.eng	Enzyme	de
dc.subject.eng	Oxidoreductase	de
dc.subject.eng	FAD	de
dc.subject.eng	Photochemistry	de
dc.subject.eng	PDH	de
dc.subject.eng	Lipoamide dehydrogenase	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0028-8818-7-0
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	869469460

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1116]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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