Funk, Lisa Marie

[["dc.bibliographiccitation.firstpage","460"],["dc.bibliographiccitation.issue","7859"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","464"],["dc.bibliographiccitation.volume","593"],["dc.contributor.author","Wensien, Marie"],["dc.contributor.author","von Pappenheim, Fabian Rabe"],["dc.contributor.author","Funk, Lisa-Marie"],["dc.contributor.author","Kloskowski, Patrick"],["dc.contributor.author","Curth, Ute"],["dc.contributor.author","Diederichsen, Ulf"],["dc.contributor.author","Uranga, Jon"],["dc.contributor.author","Ye, Jin"],["dc.contributor.author","Fang, Pan"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2021-06-01T09:41:41Z"],["dc.date.available","2021-06-01T09:41:41Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1038/s41586-021-03513-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85005"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.title","A lysine–cysteine redox switch with an NOS bridge regulates enzyme function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","609"],["dc.bibliographiccitation.issue","7775"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","613"],["dc.bibliographiccitation.volume","573"],["dc.contributor.author","Dai, Shao-Bo"],["dc.contributor.author","Funk, Lisa Marie"],["dc.contributor.author","Rabe von Pappenheim, Fabian"],["dc.contributor.author","Sautner, Viktor"],["dc.contributor.author","Paulikat, Mirko"],["dc.contributor.author","Schröder, Benjamin"],["dc.contributor.author","Uranga, Jon"],["dc.contributor.author","Mata, Ricardo A."],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2019-11-01T09:22:30Z"],["dc.date.available","2019-11-01T09:22:30Z"],["dc.date.issued","2019"],["dc.description.abstract","The underlying molecular mechanisms of cooperativity and allosteric regulation are well understood for many proteins, with haemoglobin and aspartate transcarbamoylase serving as prototypical examples1,2. The binding of effectors typically causes a structural transition of the protein that is propagated through signalling pathways to remote sites and involves marked changes on the tertiary and sometimes even the quaternary level1-5. However, the origin of these signals and the molecular mechanism of long-range signalling at an atomic level remain unclear5-8. The different spatial scales and timescales in signalling pathways render experimental observation challenging; in particular, the positions and movement of mobile protons cannot be visualized by current methods of structural analysis. Here we report the experimental observation of fluctuating low-barrier hydrogen bonds as switching elements in cooperativity pathways of multimeric enzymes. We have observed these low-barrier hydrogen bonds in ultra-high-resolution X-ray crystallographic structures of two multimeric enzymes, and have validated their assignment using computational calculations. Catalytic events at the active sites switch between low-barrier hydrogen bonds and ordinary hydrogen bonds in a circuit that consists of acidic side chains and water molecules, transmitting a signal through the collective repositioning of protons by behaving as an atomistic Newton's cradle. The resulting communication synchronizes catalysis in the oligomer. Our studies provide several lines of evidence and a working model for not only the existence of low-barrier hydrogen bonds in proteins, but also a connection to enzyme cooperativity. This finding suggests new principles of drug and enzyme design, in which sequences of residues can be purposefully included to enable long-range communication and thus the regulation of engineered biomolecules."],["dc.identifier.doi","10.1038/s41586-019-1581-9"],["dc.identifier.pmid","31534226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62552"],["dc.language.iso","en"],["dc.relation.eissn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.relation.issn","1476-4687"],["dc.title","Low-barrier hydrogen bonds in enzyme cooperativity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2580"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","ChemBioChem"],["dc.bibliographiccitation.lastpage","2584"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Wechsler, Cindy"],["dc.contributor.author","Meyer, Danilo"],["dc.contributor.author","Loschonsky, Sabrina"],["dc.contributor.author","Funk, Lisa-Marie"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:54:48Z"],["dc.date.available","2017-09-07T11:54:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Enantioselective bond making and breaking is a hallmark of enzyme action, yet switching the enantioselectivity of the reaction is a difficult undertaking, and typically requires extensive screening of mutant libraries and multiple mutations. Here, we demonstrate that mutational diversification of a single catalytic hot spot in the enzyme pyruvate decarboxylase gives access to both enantiomers of acyloins acetoin and phenylacetylcarbinol, important pharmaceutical precursors, in the case of acetoin even starting from the unselective wild-type protein. Protein crystallography was used to rationalize these findings and to propose a mechanistic model of how enantioselectivity is controlled. In a broader context, our studies highlight the efficiency of mechanism-inspired and structure-guided rational protein design for enhancing and switching enantioselectivity of enzymatic reactions, by systematically exploring the biocatalytic potential of a single hot spot."],["dc.identifier.doi","10.1002/cbic.201500529"],["dc.identifier.gro","3141766"],["dc.identifier.isi","000367720300005"],["dc.identifier.pmid","26488818"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/835"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: DFG [FOR1296]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.eissn","1439-7633"],["dc.relation.issn","1439-4227"],["dc.title","Tuning and Switching Enantioselectivity of Asymmetric Carboligation in an Enzyme through Mutational Analysis of a Single Hot Spot"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","368"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Chemical Biology"],["dc.bibliographiccitation.lastpage","375"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Rabe von Pappenheim, Fabian"],["dc.contributor.author","Wensien, Marie"],["dc.contributor.author","Ye, Jin"],["dc.contributor.author","Uranga, Jon"],["dc.contributor.author","Irisarri, Iker"],["dc.contributor.author","de Vries, Jan"],["dc.contributor.author","Funk, Lisa-Marie"],["dc.contributor.author","Mata, Ricardo A."],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2022-04-01T10:02:39Z"],["dc.date.available","2022-04-01T10:02:39Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract We recently reported the discovery of a lysine–cysteine redox switch in proteins with a covalent nitrogen–oxygen–sulfur (NOS) bridge. Here, a systematic survey of the whole protein structure database discloses that NOS bridges are ubiquitous redox switches in proteins of all domains of life and are found in diverse structural motifs and chemical variants. In several instances, lysines are observed in simultaneous linkage with two cysteines, forming a sulfur–oxygen–nitrogen–oxygen–sulfur (SONOS) bridge with a trivalent nitrogen, which constitutes an unusual native branching cross-link. In many proteins, the NOS switch contains a functionally essential lysine with direct roles in enzyme catalysis or binding of substrates, DNA or effectors, linking lysine chemistry and redox biology as a regulatory principle. NOS/SONOS switches are frequently found in proteins from human and plant pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and also in many human proteins with established roles in gene expression, redox signaling and homeostasis in physiological and pathophysiological conditions."],["dc.identifier.doi","10.1038/s41589-021-00966-5"],["dc.identifier.pii","966"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105971"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1552-4469"],["dc.relation.issn","1552-4450"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Widespread occurrence of covalent lysine–cysteine redox switches in proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11270"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","11282"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Meyer, Andreas"],["dc.contributor.author","Kehl, Annemarie"],["dc.contributor.author","Cui, Chang"],["dc.contributor.author","Reichardt, Fehmke A. K."],["dc.contributor.author","Hecker, Fabian"],["dc.contributor.author","Funk, Lisa-Marie"],["dc.contributor.author","Ghosh, Manas K."],["dc.contributor.author","Pan, Kuan-Ting"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Tittmann, Kai"],["dc.contributor.author","Bennati, Marina"],["dc.date.accessioned","2022-07-01T07:34:46Z"],["dc.date.available","2022-07-01T07:34:46Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1021/jacs.2c02906"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112011"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","1520-5126"],["dc.relation.issn","0002-7863"],["dc.title","19 F Electron-Nuclear Double Resonance Reveals Interaction between Redox-Active Tyrosines across the α/β Interface of E. coli Ribonucleotide Reductase"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]