Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","1321"],["dc.bibliographiccitation.journal","Acta Crystallographica Section D Biological Crystallography"],["dc.bibliographiccitation.lastpage","1335"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Sidhu, Navdeep S."],["dc.contributor.author","Schreiber, Kathrin"],["dc.contributor.author","Proepper, Kevin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Uson, Isabel"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 A resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder."],["dc.identifier.doi","10.1107/S1399004714002739"],["dc.identifier.gro","3142131"],["dc.identifier.isi","000335952500014"],["dc.identifier.pmid","24816101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4888"],["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","Wiley-blackwell"],["dc.relation.issn","1399-0047"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA"],["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"]]

[["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","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","773"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Genetics"],["dc.bibliographiccitation.lastpage","775"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Henneke, Marco"],["dc.contributor.author","Diekmann, Simone"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Kaiser, Jens"],["dc.contributor.author","Engelbrecht, Volkher"],["dc.contributor.author","Kohlschuetter, Alfried"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Madruga-Garrido, Marcos"],["dc.contributor.author","Mayer, Michele"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Rodriguez, Diana"],["dc.contributor.author","Rueschendorf, Franz"],["dc.contributor.author","Schumacher, Johannes"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2009"],["dc.description.abstract","Congenital cytomegalovirus brain infection without symptoms at birth can cause a static encephalopathy with characteristic patterns of brain abnormalities. Here we show that loss-of-function mutations in the gene encoding the RNASET2 glycoprotein lead to cystic leukoencephalopathy, an autosomal recessive disorder with an indistinguishable clinical and neuroradiological phenotype. Congenital cytomegalovirus infection and RNASET2 deficiency may both interfere with brain development and myelination through angiogenesis or RNA metabolism."],["dc.identifier.doi","10.1038/ng.398"],["dc.identifier.gro","3143090"],["dc.identifier.isi","000267786200005"],["dc.identifier.pmid","19525954"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6147"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/565"],["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","Nature Publishing Group"],["dc.relation.issn","1061-4036"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","988"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","998"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Reinhardt, Konstanze"],["dc.contributor.author","Schreiber, Kathrin"],["dc.contributor.author","Hillebrand, Merle"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:52:41Z"],["dc.date.available","2017-09-07T11:52:41Z"],["dc.date.issued","2006"],["dc.description.abstract","Cathepsin D is a ubiquitously expressed lysosomal protease that is involved in proteolytic degradation, cell invasion, and apoptosis. In mice and sheep, cathepsin D deficiency is known to cause a fatal neurodegenerative disease. Here, we report a novel disorder in a child with early blindness and progressive psychomotor disability. Two missense mutations in the CTSD gene, F229I and W383C, were identified and were found to cause markedly reduced proteolytic activity and a diminished amount of cathepsin D in patient fibroblasts. Expression of cathepsin D mutants in cathepsin D-/- mouse fibroblasts revealed disturbed posttranslational processing and intracellular targeting for W383C and diminished maximal enzyme velocity for F229I. The structural effects of cathepsin D mutants were estimated by computer modeling, which suggested larger structural alterations for W383C than for F229I. Our studies broaden the group of human neurodegenerative disorders and add new insight into the cellular functions of human cathepsin D."],["dc.identifier.doi","10.1086/504159"],["dc.identifier.gro","3143679"],["dc.identifier.isi","000237553800008"],["dc.identifier.pmid","16685649"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1219"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Univ Chicago Press"],["dc.relation.issn","0002-9297"],["dc.title","Cathepsin D deficiency is associated with a human neurodegenerative disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","379"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","European Journal of Pediatrics"],["dc.bibliographiccitation.lastpage","380"],["dc.bibliographiccitation.volume","168"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Pal, Aritra"],["dc.contributor.author","Gruene, Tim"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Sheldrick, George M."],["dc.date.accessioned","2018-11-07T08:31:59Z"],["dc.date.available","2018-11-07T08:31:59Z"],["dc.date.issued","2009"],["dc.identifier.isi","000262826600042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17243"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.issn","0340-6199"],["dc.title","The 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.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"]]