Neumann, Piotr D.

[["dc.bibliographiccitation.firstpage","88"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Molecular Catalysis B Enzymatic"],["dc.bibliographiccitation.lastpage","92"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Weidner, Annett"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Pech, Andreas"],["dc.contributor.author","Stubbs, Milton T."],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2018-11-07T11:22:52Z"],["dc.date.available","2018-11-07T11:22:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Pyruvate oxidase from Escherichia coli (EcPOX) is a thiamin diphosphate- (ThDP) and FAD-dependent peripheral membrane protein that carries out the irreversible oxidative decarboxylation of pyruvate to acetate and carbon dioxide. Concomitant two-electron reduction of the flavin cofactor was suggested to induce a Structural rearrangement of the C-terminus triggering recruitment of the protein from the cytosol to the cell membrane, where the electrons are eventually transferred to final electron acceptor ubiquinone 8. Binding to the membrane, or alternatively, mild proteolytic digestion leads to a multifold enhancement of both the catalytic activity and substrate affinity. Recent X-ray crystallographic studies on EcPOX in the resting state and on a C-terminal truncation variant mimicking the membrane-bound activated form have fueled our understanding of the membrane-binding mechanism and concomitant catalytic activation. In the resting state, the auto-inhibitory C-terminal membrane anchor adopts a half-barrel/helix fold that occludes the active site. Upon activation, the C-terminus is expelled and becomes structurally flexible thereby freeing the active site. Circular dichroism spectroscopic analysis revealed the isolated C-terminus to be disordered, however, formation of a helical structure was observed in the presence of micelles. Limited proteolysis experiments indicate that activation of EcPOX involves at least two sequential structural transitions: the first occurring after binding of pyruvate to ThDP and the second after two-electron reduction of the flavin. (C) 2009 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.molcatb.2009.02.020"],["dc.identifier.isi","000271169600015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56068"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","International Conference on Mechanisms and Physiology of Thiamine"],["dc.relation.eventlocation","Wittenberg, GERMANY"],["dc.relation.issn","1381-1177"],["dc.title","New insights into the membrane-binding and activation mechanism of pyruvate oxidase from Escherichia coli"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","488"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Nature Chemical Biology"],["dc.bibliographiccitation.lastpage","U84"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Meyer, Danilo"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:47:38Z"],["dc.date.available","2017-09-07T11:47:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Carbenes are highly reactive chemical compounds that are exploited as ligands in organometallic chemistry and are powerful organic catalysts. They were postulated to occur as transient intermediates in enzymes, yet their existence in a biological system could never be demonstrated directly. We present spectroscopic and structural data of a thiamin enzyme in a noncovalent complex with substrate, which implicate accumulation of a stable carbene as a major resonance contributor to deprotonated thiamin."],["dc.identifier.doi","10.1038/nchembio.1275"],["dc.identifier.gro","3142316"],["dc.identifier.isi","000321952700006"],["dc.identifier.pmid","23748673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6931"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [SFB 860/B07, FOR 1296/TP3]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1552-4450"],["dc.title","Observation of a stable carbene at the active site of a thiamin enzyme"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","122"],["dc.bibliographiccitation.journal","Current Opinion in Structural Biology"],["dc.bibliographiccitation.lastpage","133"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:45:22Z"],["dc.date.available","2017-09-07T11:45:22Z"],["dc.date.issued","2014"],["dc.description.abstract","Although general principles of enzyme catalysis are fairly well understood nowadays, many important details of how exactly the substrate is bound and processed in an enzyme remain often invisible and as such elusive. In fortunate cases, structural analysis of enzymes can be accomplished at true atomic resolution thus making possible to shed light on otherwise concealed fine-structural traits of bound substrates, intermediates, cofactors and protein groups. We highlight recent structural studies of enzymes using ultrahigh-resolution X-ray protein crystallography showcasing its enormous potential as a tool in the elucidation of enzymatic mechanisms and in unveiling fundamental principles of enzyme catalysis. We discuss the observation of seemingly hyperreactive, physically distorted cofactors and intermediates with elongated scissile substrate bonds, the detection of 'hidden' conformational and chemical equilibria and the analysis of protonation states with surprising findings. In delicate cases, atomic resolution is required to unambiguously disclose the identity of atoms as demonstrated for the metal cluster in nitrogenase. In addition to the pivotal structural findings and the implications for our understanding of enzyme catalysis, we further provide a practical framework for resolution enhancement through optimized data acquisition and processing."],["dc.identifier.doi","10.1016/j.sbi.2014.11.001"],["dc.identifier.gro","3142002"],["dc.identifier.isi","000348016600017"],["dc.identifier.pmid","25460275"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3457"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Current Biology Ltd"],["dc.relation.eissn","1879-033X"],["dc.relation.issn","0959-440X"],["dc.title","Marvels of enzyme catalysis at true atomic resolution: distortions, bond elongations, hidden flips, protonation states and atom identities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","10867"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","10872"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Meyer, Danilo"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Koers, Eline"],["dc.contributor.author","Sjuts, Hanno"],["dc.contributor.author","Lüdtke, Stefan"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:48:50Z"],["dc.date.available","2017-09-07T11:48:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Thiamin diphosphate, the vitamin B1 coenzyme, plays critical roles in fundamental metabolic pathways that require acyl carbanion equivalents. Studies on chemical models and enzymes had suggested that these carbanions are resonance-stabilized as enamines. A crystal structure of this intermediate in pyruvate oxidase at 1.1 angstrom resolution now challenges this paradigm by revealing that the enamine does not accumulate. Instead, the intermediate samples between the ketone and the carbanion both interlocked in a tautomeric equilibrium. Formation of the keto tautomer is associated with a loss of aromaticity of the cofactor. The alternate confinement of electrons to neighboring atoms rather than pi-conjugation seems to be of importance for the enzyme-catalyzed, redox-coupled acyl transfer to phosphate, which requires a dramatic inversion of polarity of the reacting substrate carbon in two subsequent catalytic steps. The ability to oscillate between a nucleophilic (carbanion) and an electrophilic (ketone) substrate center highlights a hitherto unrecognized versatility of the thiamin cofactor. It remains to be studied whether formation of the keto tautomer is a general feature of all thiamin enzymes, as it could provide for stable storage of the carbanion state, or whether this feature represents a specific trait of thiamin oxidases. In addition, the protonation state of the two-electron reduced flavin cofactor can be fully assigned, demonstrating the power of high-resolution cryocrystallography for elucidation of enzymatic mechanisms."],["dc.identifier.doi","10.1073/pnas.1201280109"],["dc.identifier.gro","3142497"],["dc.identifier.isi","000306641100036"],["dc.identifier.pmid","22730460"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8855"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Unexpected tautomeric equilibria of the carbanion-enamine intermediate in pyruvate oxidase highlight unrecognized chemical versatility of thiamin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8197"],["dc.bibliographiccitation.issue","37"],["dc.bibliographiccitation.journal","Biochemistry"],["dc.bibliographiccitation.lastpage","8212"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Meyer, Danilo"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Parthier, Christoph"],["dc.contributor.author","Friedemann, Rudolf"],["dc.contributor.author","Nemeria, Natalia"],["dc.contributor.author","Jordan, Frank"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2018-11-07T08:39:07Z"],["dc.date.available","2018-11-07T08:39:07Z"],["dc.date.issued","2010"],["dc.description.abstract","Pyruvate decarboxylase (PDC) catalyzes the nonoxidative decarboxylation of pyruvate into acetaldehyde and carbon dioxide and requires thiamin diphosphate (ThDP) and a divalent cation as cofactors. Recent studies have permitted the assignment of functional roles of active site residues; however, the underlying reaction mechanisms of elementary steps have remained hypothetical. Here, a kinetic and thermodynamic single-step analysis in conjunction with X-ray crystallographic studies of PDC from Zymomonas mobilis implicates active site residue Glu473 (located on the re-face of the ThDP thiazolium nucleus) in facilitating both decarboxylation of 2-lactyl-ThDP and protonation of the 2-hydroxyethyl-ThDP carbanion/enamine intermediate. Variants carrying either an isofunctional (Glu473Asp) or isosteric (Glu473Gln) substitution exhibit a residual catalytic activity of less than 0.1% but accumulate different intermediates at the steady state. Whereas the predecarboxylation intermediate 2-lactyl-ThDP is accumulated in Glu473Asp because of a 3000-fold slower decarboxylation compared to that of the wild-type enzyme, Glu473GIn is not impaired in decarboxylation but generates a long-lived 2-hydroxyethyl-ThDP carbanion/enamine postdecarboxylation intermediate. CD spectroscopic analysis of the protonic and tautomeric equilibria of the cocatalytic aminopyrimidine part of ThDP indicates that an acidic residue is required at position 473 for proper substrate binding. Wild-type PDC and the Glu473Asp variant bind the substrate analogue acetylphosphinate with the same affinity; implying a similar stabilization of the predecarboxylation intermediate analogue on the enzyme, whereas Glu473GIn fails to bind the analogue. The X-ray crystallographic structure of 2-lactyl-ThDP trapped in the decarboxylation-deficient variant Glu473Asp reveals a common stereochemistry of the intermediate C2 alpha stereocenter; however, the scissile C2 alpha-C(carboxylate) bond deviates by 25-30 from the perpendicular \"maximum overlap\" orientation relative to the thiazolium ring plane as commonly observed in ThDP enzymes. Because a reactant-state stabilization of the predecarboxylation intermediate can be excluded to account for the slower decarboxylation, the data suggest a strong stereoelectronic effect for the transition state of decarboxylation as supported by additional DFT studies on models. To the best of our knowledge, this is a very rare example in which the magnitude of a stereoelectronic effect could be experimentally estimated for an enzymatic system. Given that variant Glu473GIn is not decarboxylation-deficient, electrostatic stress can be excluded as a driving force for decarboxylation. The apparent dual function of Glu473 further suggests that decarboxylation and protonation of the incipient carbanion are committed and presumably proceed in the same transition state."],["dc.identifier.doi","10.1021/bi100828r"],["dc.identifier.isi","000281710500025"],["dc.identifier.pmid","20715795"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18914"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0006-2960"],["dc.title","Double Duty for a Conserved Glutamate in Pyruvate Decarboxylase: Evidence of the Participation in Stereoelectronically Controlled Decarboxylation and in Protonation of the Nascent Carbanion/Enamine Intermediate"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3069"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","3080"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Gundlach, Jan"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Schröder-Tittmann, Kathrin"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Kaesler, Jan"],["dc.contributor.author","Kampf, Jan"],["dc.contributor.author","Herzberg, Christina"],["dc.contributor.author","Hammer, Elke"],["dc.contributor.author","Schwede, Frank"],["dc.contributor.author","Kaever, Volkhard"],["dc.contributor.author","Tittmann, Kai"],["dc.contributor.author","Stülke, Jörg"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:44:39Z"],["dc.date.available","2017-09-07T11:44:39Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Cyclic di-AMP is an essential second messenger in eubacteria. Results: The c-di-AMP receptor DarA was identified in B. subtilis. The crystal structure and ITC data revealed the nucleotide specificity of DarA. Conclusion: DarA is a P-II-like protein that undergoes conformational changes upon c-di-AMP binding. Significance: A novel P-II-like protein is involved in c-di-AMP signaling. The cyclic dimeric AMP nucleotide c-di-AMP is an essential second messenger in Bacillus subtilis. We have identified the protein DarA as one of the prominent c-di-AMP receptors in B. subtilis. Crystal structure analysis shows that DarA is highly homologous to P-II signal transducer proteins. In contrast to P-II proteins, the functionally important B- and T-loops are swapped with respect to their size. DarA is a homotrimer that binds three molecules of c-di-AMP, each in a pocket located between two subunits. We demonstrate that DarA is capable to bind c-di-AMP and with lower affinity cyclic GMP-AMP (33-cGAMP) but not c-di-GMP or 23-cGAMP. Consistently the crystal structure shows that within the ligand-binding pocket only one adenine is highly specifically recognized, whereas the pocket for the other adenine appears to be promiscuous. Comparison with a homologous ligand-free DarA structure reveals that c-di-AMP binding is accompanied by conformational changes of both the fold and the position of the B-loop in DarA."],["dc.identifier.doi","10.1074/jbc.M114.619619"],["dc.identifier.gro","3141969"],["dc.identifier.isi","000349310700043"],["dc.identifier.pmid","25433025"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3090"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft [HI 291/13-1, SFB860]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Identification, Characterization, and Structure Analysis of the Cyclic di-AMP-binding P-II-like Signal Transduction Protein DarA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","17390"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","17395"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Weidner, Annett"],["dc.contributor.author","Pech, Andreas"],["dc.contributor.author","Stubbs, Milton T."],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2018-11-07T11:09:09Z"],["dc.date.available","2018-11-07T11:09:09Z"],["dc.date.issued","2008"],["dc.description.abstract","The thiamin- and flavin-dependent peripheral membrane enzyme pyruvate oxidase from E. coli catalyzes the oxidative decarboxylation of the central metabolite pyruvate to CO2 and acetate. Concomitant reduction of the enzyme-bound flavin triggers membrane binding of the C terminus and shuttling of 2 electrons to ubiquinone 8, a membrane-bound mobile carrier of the electron transport chain. Binding to the membrane in vivo or limited proteolysis in vitro stimulate the catalytic proficiency by 2 orders of magnitude. The molecular mechanisms by which membrane binding and activation are governed have remained enigmatic. Here, we present the X-ray crystal structures of the full-length enzyme and a proteolytically activated truncation variant lacking the last 23 C-terminal residues inferred as important in membrane binding. In conjunction with spectroscopic results, the structural data pinpoint a conformational rearrangement upon activation that exposes the autoinhibitory C terminus, thereby freeing the active site. In the activated enzyme, Phe-465 swings into the active site and wires both cofactors for efficient electron transfer. The isolated C terminus, which has no intrinsic helix propensity, folds into a helical structure in the presence of micelles."],["dc.identifier.doi","10.1073/pnas.0805027105"],["dc.identifier.isi","000260981800042"],["dc.identifier.pmid","18988747"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52944"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","762"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Chemistry"],["dc.bibliographiccitation.lastpage","767"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Lüdtke, Stefan"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Erixon, Karl M."],["dc.contributor.author","Leeper, Finian"],["dc.contributor.author","Kluger, Ronald"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:47:37Z"],["dc.date.available","2017-09-07T11:47:37Z"],["dc.date.issued","2013"],["dc.description.abstract","It is recognized widely that enzymes promote reactions by providing a pathway that proceeds through a transition state of lower energy. In principle, further rate enhancements could be achieved if intermediates are prevented from relaxing to their lowest energy state, and thereby reduce the barrier to the subsequent transition state. Here, we report sub-angstrom-resolution crystal structures of genuine covalent reaction intermediates of transketolase. These structures reveal a pronounced out-of-plane distortion of over 20 degrees for the covalent bond that links cofactor and substrate, and a specific elongation of the scissile substrate carbon-carbon bond (d > 1.6 angstrom). To achieve these distortions, the protein's conformation appears to prevent relaxation of a substrate-cofactor intermediate. The results implicate a reduced barrier to the subsequent step that is consistent with an intermediate of raised energy and leads to a more efficient overall process."],["dc.identifier.doi","10.1038/NCHEM.1728"],["dc.identifier.gro","3142294"],["dc.identifier.isi","000323616700012"],["dc.identifier.pmid","23965678"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6687"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1755-4330"],["dc.title","Sub-ångström-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic intermediate"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","678"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Nature Chemical Biology"],["dc.bibliographiccitation.lastpage","684"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Lehwess-Litzmann, Anja"],["dc.contributor.author","Neumann, Piotr"],["dc.contributor.author","Parthier, Christoph"],["dc.contributor.author","Luedtke, Stefan"],["dc.contributor.author","Golbik, Ralph"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Tittmann, Kai"],["dc.date.accessioned","2017-09-07T11:43:24Z"],["dc.date.available","2017-09-07T11:43:24Z"],["dc.date.issued","2011"],["dc.description.abstract","We examined the catalytic cycle of transaldolase (TAL) from Thermoplasma acidophilum by cryocrystallography and were able to structurally characterize-for the first time, to our knowledge-different genuine TAL reaction intermediates. These include the Schiff base adducts formed between the catalytic lysine and the donor ketose substrates fructose-6-phosphate and sedoheptulose-7-phosphate as well as the Michaelis complex with acceptor aldose erythrose-4-phosphate. These structural snapshots necessitate a revision of the accepted reaction mechanism with respect to functional roles of active site residues, and they further reveal fundamental insights into the general structural features of enzymatic Schiff base intermediates and the role of conformational dynamics in enzyme catalysis, substrate binding and discrimination. A nonplanar arrangement of the substituents around the Schiff base double bond was observed, suggesting that a structurally encoded reactant-state destabilization is a driving force of catalysis. Protein dynamics and the intrinsic hydrogen-bonding pattern appear to be crucial for selective recognition and binding of ketose as first substrate."],["dc.identifier.doi","10.1038/NCHEMBIO.633"],["dc.identifier.gro","3142663"],["dc.identifier.isi","000295027100011"],["dc.identifier.pmid","21857661"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1552-4450"],["dc.title","Twisted Schiff base intermediates and substrate locale revise transaldolase mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]