Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","2100"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","2106"],["dc.contributor.author","Pitulescu, Marian"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Knepel, Willhart"],["dc.contributor.author","Diederichsen, Ulf"],["dc.date.accessioned","2018-11-07T11:16:29Z"],["dc.date.available","2018-11-07T11:16:29Z"],["dc.date.issued","2008"],["dc.description.abstract","Two formacetal-linked dinucleotides TT and TT were synthesized as phosphoramidite building blocks for solid-phase synthesis. Incorporated in a 29-mer DNA, the oligomers P3(TT) and P3(TA) were studied with respect to the binding activity towards the Pax6 homeodomain. Substitution of the negatively charged phosphodiester by a neutral formacetal linker facilitates the bent conformation of double-stranded DNA. The duplex stability was affected more significantly by the TT formacetal modification, whereas destabilization induced by TA was less pronounced. Based on CD spectroscopy, the TA formacetal-modified oligomer P3(TA) A has mainly B-DNA topology, whereas the P3(TT) modified oligomet significantly deviated from B-form DNA. The binding affinity of the P3 oligomer towards Pax6 HD was investigated by in vitro EMSA experiments providing even a small increase in binding affinity for the P3(TA) T oligomer. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)."],["dc.identifier.doi","10.1002/ejoc.200701178"],["dc.identifier.isi","000255508600010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54599"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis of formacetal-linked dinucleotides to facilitate dsDNA bending and binding to the homeodomain of Pax6"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Pal, A."],["dc.contributor.author","Grune, Tim"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Schreiber, K."],["dc.contributor.author","Gaertner, J."],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2018-11-07T08:40:54Z"],["dc.date.available","2018-11-07T08:40:54Z"],["dc.date.issued","2010"],["dc.format.extent","S141"],["dc.identifier.isi","000281735000448"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19348"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Dordrecht"],["dc.relation.issn","0141-8955"],["dc.title","STRUCTURE OF TRIPEPTIDYL-PEPTIDASE I (TPP1) PROVIDES INSIGHT INTO THE MOLECULAR BASIS OF LATE INFANTILE NEURONAL CEROID LIPOFUSCINOSIS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Dreha-Kulaczewski, S. F."],["dc.contributor.author","Wevers, Ron A."],["dc.contributor.author","Gaertner, J."],["dc.date.accessioned","2018-11-07T08:40:55Z"],["dc.date.available","2018-11-07T08:40:55Z"],["dc.date.issued","2010"],["dc.format.extent","S158"],["dc.identifier.isi","000281735000507"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19350"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Dordrecht"],["dc.relation.issn","0141-8955"],["dc.title","CEREBRAL FOLATE TRANSPORT DEFICIENCY: A NOVEL INHERITED DISORDER OF FOLATE METABOLISM"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","403"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms"],["dc.bibliographiccitation.lastpage","412"],["dc.bibliographiccitation.volume","1789"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Teichler, Sabine"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Dickel, Corinna"],["dc.contributor.author","Knepel, Willhart"],["dc.contributor.author","Kraetzner, Ralph"],["dc.date.accessioned","2018-11-07T08:30:08Z"],["dc.date.available","2018-11-07T08:30:08Z"],["dc.date.issued","2009"],["dc.description.abstract","The transcription factor PAX6 plays an important role in transcriptional regulation of the peptide hormone glucagon from pancreatic alpha-cells. PAX6 contains two DNA binding domains, the paired domain (PD) and the homeodomain (HD). While the interaction of the PD with the PAX6 responsive elements G1 and G3 in the rat glucagon gene promoter is well understood, the role of the PAX6 HD for PAX6 binding and function on G1 and G3 remains unclear. In EMSA studies the PAX6 HD was found to be mandatory for PAX6 binding to G1 but not to G3. Transient transfections with luciferase reporter gene constructs revealed the HD to be critical for proper function of PAX6 on both, G1 and G3. Transfection data with variant promoter constructs and limited proteolysis assays demonstrated that the DNA sequence located 5' to the PD binding site plays an important role for PAX6 function and its conformation on the elements G1 and G3. Taken together, our data indicate a PH0-like binding of PAX6 to the glucagon promoter elements G1 and G3 where the HD binding site is abutted directly to the PD binding motif The data suggest that the PH0-like binding induces a transcriptionally active conformation of PAX6. (C) 2009 Elsevier B.V. All rights reserved."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB402/A3]"],["dc.identifier.doi","10.1016/j.bbagrm.2009.02.001"],["dc.identifier.isi","000267466400004"],["dc.identifier.pmid","19217949"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16821"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1874-9399"],["dc.title","The homeodomain of PAX6 is essential for PAX6-dependent activation of the rat glucagon gene promoter: Evidence for a PH0-like binding that induces an active conformation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","372"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kratzner, R."],["dc.contributor.author","Teichler, S."],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T10:14:51Z"],["dc.date.available","2018-11-07T10:14:51Z"],["dc.date.issued","2006"],["dc.format.extent","71"],["dc.identifier.isi","000237126800258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40702"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","47th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Role of the PAX6 homeodomain in regulation of glucagon gene transcrition"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3976"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","3984"],["dc.bibliographiccitation.volume","284"],["dc.contributor.author","Pal, Aritra"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Gruene, Tim"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Schreiber, Kathrin"],["dc.contributor.author","Gronborg, Mads"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2017-09-07T11:47:33Z"],["dc.date.available","2017-09-07T11:47:33Z"],["dc.date.issued","2009"],["dc.description.abstract","Late infantile neuronal ceroid lipofuscinosis, a fatal neurodegenerative disease of childhood, is caused by mutations in the TPP1 gene that encodes tripeptidyl-peptidase I. We show that purified TPP1 requires at least partial glycosylation for in vitro autoprocessing and proteolytic activity. We crystallized the fully glycosylated TPP1 precursor under conditions that implied partial autocatalytic cleavage between the prosegment and the catalytic domain. X-ray crystallographic analysis at 2.35 angstrom resolution reveals a globular structure with a subtilisin-like fold, a Ser(475) -Glu(272) -Asp(360) catalytic triad, and an octahedrally coordinated Ca(2+) -binding site that are characteristic features of the S53 sedolisin family of peptidases. In contrast to other S53 peptidases, the TPP1 structure revealed steric constraints on the P4 substrate pocket explaining its preferential cleavage of tripeptides from the unsubstituted N terminus of proteins. Two alternative conformations of the catalytic Asp(276) are associated with the activation status of TPP1. 28 disease-causing missense mutations are analyzed in the light of the TPP1 structure providing insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis."],["dc.identifier.doi","10.1074/jbc.M806947200"],["dc.identifier.gro","3143151"],["dc.identifier.isi","000262872500066"],["dc.identifier.pmid","19038966"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/633"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Fonds der Chemischen Industrie"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Structure of Tripeptidyl-peptidase I Provides Insight into the Molecular Basis of Late Infantile Neuronal Ceroid Lipofuscinosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-11-07T09:00:10Z"],["dc.date.available","2018-11-07T09:00:10Z"],["dc.date.issued","2011"],["dc.format.extent","S119"],["dc.identifier.isi","000309837800148"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24087"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Dordrecht"],["dc.relation.issn","0141-8955"],["dc.title","THE EXTENDED CLINICAL SPECTRUM OF CEREBRAL FOLATE TRANSPORT DEFICIENCY"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","354"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","363"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Helms, Gunther"],["dc.contributor.author","Dechent, Peter"],["dc.contributor.author","Wevers, Ron"],["dc.contributor.author","Grosso, Salvatore"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-07-09T11:52:56Z"],["dc.date.available","2019-07-09T11:52:56Z"],["dc.date.issued","2009"],["dc.description.abstract","Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency.We identified an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRa). Three patients carrying FOLR1 mutations developed progressive movement disturbance, psychomotor decline, and epilepsy and showed severely reduced folate concentrations in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) demonstrated profound hypomyelination, and MR-based in vivo metabolite analysis indicated a combined depletion of white-matter choline and inositol. Retroviral transfection of patient cells with either FRa or FRb could rescue folate binding. Furthermore, CSF folate concentrations, as well as glial choline and inositol depletion, were restored by folinic acid therapy and preceded clinical improvements. Our studies not only characterize a previously unknown and treatable disorder of early childhood, but also provide new insights into the folate metabolic pathways involved in postnatal myelination and brain development."],["dc.identifier.doi","10.1016/j.ajhg.2009.08.005."],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60304"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Folate Receptor Alpha Defect Causes Cerebral Folate Transport Deficiency: A Treatable Neurodegenerative Disorder Associated with Disturbed Myelin Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8733"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","8742"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Thorn, Andrea"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Ziegenbein, Marc"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.date.accessioned","2017-09-07T11:48:25Z"],["dc.date.available","2017-09-07T11:48:25Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in the gene of human RNase T2 are associated with white matter disease of the human brain. Although brain abnormalities (bilateral temporal lobe cysts and multifocal white matter lesions) and clinical symptoms (psychomotor impairments, spasticity and epilepsy) are well characterized, the pathomechanism of RNase T2 deficiency remains unclear. RNase T2 is the only member of the Rh/T2/S family of acidic hydrolases in humans. In recent years, new functions such as tumor suppressing properties of RNase T2 have been reported that are independent of its catalytic activity. We determined the X-ray structure of human RNase T2 at 1.6 A resolution. The alpha+beta core fold shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences. The catalytic features of RNase T2 in presence of bivalent cations were analyzed and the structural consequences of known clinical mutations were investigated. Our data provide further insight into the function of human RNase T2 and may prove useful in understanding its mode of action independent of its enzymatic activity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1093/nar/gks614"],["dc.identifier.gro","3142467"],["dc.identifier.isi","000309464300054"],["dc.identifier.pmid","22735700"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7944"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8607"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0305-1048"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure and activity of the only human RNase T2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]