Hildmann, Christian

[["dc.bibliographiccitation.firstpage","202"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Analytical Biochemistry"],["dc.bibliographiccitation.lastpage","208"],["dc.bibliographiccitation.volume","321"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:50:01Z"],["dc.date.available","2021-06-01T10:50:01Z"],["dc.date.issued","2003"],["dc.identifier.doi","10.1016/S0003-2697(03)00426-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86498"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0003-2697"],["dc.title","Improved fluorogenic histone deacetylase assay for high-throughput-screening applications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","270"],["dc.bibliographiccitation.journal","Acta Crystallographica Section F Structural Biology and Crystallization Communications"],["dc.bibliographiccitation.lastpage","273"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Nielsen, Tine Kragh"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:49:48Z"],["dc.date.available","2017-09-07T11:49:48Z"],["dc.date.issued","2007"],["dc.description.abstract","Histone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with a nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme-inhibitor binding."],["dc.identifier.doi","10.1107/S1744309107012377"],["dc.identifier.gro","3143512"],["dc.identifier.isi","000245505800004"],["dc.identifier.pmid","17401192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1034"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","1744-3091"],["dc.title","Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3005"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Bioinformatics"],["dc.bibliographiccitation.lastpage","3012"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Lewin, J."],["dc.contributor.author","Schmitt, A. O."],["dc.contributor.author","Adorjan, P."],["dc.contributor.author","Hildmann, T."],["dc.contributor.author","Piepenbrock, C."],["dc.date.accessioned","2022-06-08T07:59:06Z"],["dc.date.available","2022-06-08T07:59:06Z"],["dc.date.issued","2004"],["dc.identifier.doi","10.1093/bioinformatics/bth346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/110633"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-575"],["dc.relation.eissn","1460-2059"],["dc.relation.issn","1367-4803"],["dc.title","Quantitative DNA methylation analysis based on four-dye trace data from direct sequencing of PCR amplificates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","451"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular Genetics and Metabolism"],["dc.bibliographiccitation.lastpage","462"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Wirsching, Frank"],["dc.contributor.author","Keller, Martina"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:50:00Z"],["dc.date.available","2021-06-01T10:50:00Z"],["dc.date.issued","2003"],["dc.identifier.doi","10.1016/j.ymgme.2003.09.007"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86486"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","1096-7192"],["dc.title","Directed evolution towards protease-resistant hirudin variants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3651"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Bioorganic & Medicinal Chemistry Letters"],["dc.bibliographiccitation.lastpage","3656"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Haus, Patricia"],["dc.contributor.author","Galetovic, Antonia"],["dc.contributor.author","Schober, Andreas"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Meyer-Almes, Franz-Josef"],["dc.date.accessioned","2018-11-07T08:28:00Z"],["dc.date.available","2018-11-07T08:28:00Z"],["dc.date.issued","2009"],["dc.description.abstract","Histone deacetylases reside among the most important and novel target classes in oncology. Selective lead structures are intensively developed to improve efficacy and reduce adverse effects. The common assays used so far to identify new lead structures suffer from many false positive hits due to auto-fluorescence of compounds or triggering undesired signal transduction pathways. These drawbacks are eliminated by the dual parameter competition assay reported in this study. The assay involves a new fluorescent inhibitor probe that shows an increase in both, fluorescence anisotropy and fluorescence lifetime upon binding to the enzyme. The assay is well suited for high-throughput screening. (C) 2009 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.bmcl.2009.04.102"],["dc.identifier.isi","000266822800064"],["dc.identifier.pmid","19457659"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16324"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","1464-3405"],["dc.relation.issn","0960-894X"],["dc.title","Non-isotopic dual parameter competition assay suitable for high-throughput screening of histone deacetylases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","439"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","445"],["dc.bibliographiccitation.volume","357"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Gruenewald, Sylvia"],["dc.contributor.author","Beckers, Thomas"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2018-11-07T11:01:37Z"],["dc.date.available","2018-11-07T11:01:37Z"],["dc.date.issued","2007"],["dc.description.abstract","Historic deacetylases (HDACs) catalyze the deacetylation of epsilon-acetyl-lysine residues within the N-terminal tail of core histones and thereby mediate changes in the chromatin structure and regulate gene expression in eukaryotic cells. So far, surprisingly little is known about the substrate specificities of different HDACs. Here, we prepared a library of fluorogenic tripeptidic substrates of the general format Ac-P-2-P-1-Lys(Ac)-MCA (P-1, P-2 = all amino acids except cysteine) and measured their HDAC-dependent conversion in a standard fluorogenic HDAC assay. Different HDAC subtypes can be ranked according to their substrate selectivity: HDAH > HDAC8 > HDAC1 > HDAC3 > HDAC6. HDAC1, HDAC3, and HDAC6 exhibit a similar specificity profile, whereas both HDAC8 and HDAH have rather distinct profiles. Furthermore, it was shown that second-site modification (e.g., phosphorylation) of substrate sequences as well as corepressor binding can modulate the selectivity of enzymatic substrate conversion. (c) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bbrc.2007.03.158"],["dc.identifier.isi","000246253700019"],["dc.identifier.pmid","17428445"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51188"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0006-291X"],["dc.title","Factors affecting the substrate specificity of histone deacetylases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","258"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.lastpage","270"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hempel, Rene"],["dc.contributor.author","Schober, Andreas"],["dc.contributor.author","Merana, Joachim"],["dc.contributor.author","Giurato, Laura"],["dc.contributor.author","Guccione, Salvatore"],["dc.contributor.author","Nielsen, Tine Kragh"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2017-09-07T11:52:42Z"],["dc.date.available","2017-09-07T11:52:42Z"],["dc.date.issued","2006"],["dc.description.abstract","Histone deacetylases (HDACs) are key enzymes in the transcriptional regulation of gene expression in eukaryotic cells. In recent years MACs have attracted considerable attention as promising new targets in anticancer therapy. Currently, different histone deacetylase subtypes are divided into four groups denoted as classes 1-4. Here, we compare in more detail representatives of class I HDACs and FB188 HDAH as a close bacterial homologue of class 2 HDAC6, in regard of substrate and inhibitor specificity. Structure comparison is used to identify candidate regions responsible for observed specificity differences. Knowledge of these structural elements expedite studies on the biochemical role of different HDAC subtypes as well as the development of highly selective HDAC inhibitors as antitumor agents. (c) 2006 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jbiotec.2006.01.030"],["dc.identifier.gro","3143672"],["dc.identifier.isi","000238620900022"],["dc.identifier.pmid","16567013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1211"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eissn","1873-4863"],["dc.relation.eventlocation","Wiesbaden, GERMANY"],["dc.relation.ispartof","Journal of Biotechnology"],["dc.relation.issn","0168-1656"],["dc.title","Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Klinische Pädiatrie"],["dc.bibliographiccitation.volume","219"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Deubzer, Hedwig E."],["dc.contributor.author","Oehme, I."],["dc.contributor.author","Hildmann, C."],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Witt, Olaf"],["dc.date.accessioned","2018-11-07T11:02:52Z"],["dc.date.available","2018-11-07T11:02:52Z"],["dc.date.issued","2007"],["dc.format.extent","195"],["dc.identifier.isi","000247267800083"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51487"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.publisher.place","Stuttgart"],["dc.relation.issn","0300-8630"],["dc.title","A novel HDAC inhibitor identified in the screening of a compound library is effective in neuroblastoma cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","659"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biochemical Journal"],["dc.bibliographiccitation.lastpage","665"],["dc.bibliographiccitation.volume","401"],["dc.contributor.author","Moreth, Kristin"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Hempel, René"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Schober, Andreas"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:50:54Z"],["dc.date.available","2021-06-01T10:50:54Z"],["dc.date.issued","2007"],["dc.description.abstract","HDACs (histone deacetylases) are considered to be among the most important enzymes that regulate gene expression in eukaryotic cells acting through deacetylation of ϵ-acetyl-lysine residues within the N-terminal tail of core histones. In addition, both eukaryotic HDACs as well as their bacterial counterparts were reported to also act on non-histone targets. However, we are still far from a comprehensive understanding of the biological activities of this ancient class of enzymes. In the present paper, we studied in more detail the esterase activity of HDACs, focussing on the HDAH (histone deacetylase-like amidohydrolase) from Bordetella/Alcaligenes strain FB188. This enzyme was classified as a class 2 HDAC based on sequence comparison as well as functional data. Using chromogenic and fluorogenic ester substrates we show that HDACs such as FB188 HDAH indeed have esterase activity that is comparable with those of known esterases. Similar results were obtained for human HDAC1, 3 and 8. Standard HDAC inhibitors were able to block both activities with similar IC50 values. Interestingly, HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA) also showed inhibitory activity against porcine liver esterase and Pseudomonas fluorescens lipase. The esterase and the amidohydrolase activity of FB188 HDAH both appear to have the same substrate specificity concerning the acyl moiety. Interestingly, a Y312F mutation in the active site of HDAH obstructed amidohydrolase activity but significantly improved esterase activity, indicating subtle differences in the mechanism of both catalytic activities. Our results suggest that, in principle, HDACs may have other biological roles besides acting as protein deacetylases. Furthermore, data on HDAC inhibitors affecting known esterases indicate that these molecules, which are currently among the most promising drug candidates in cancer therapy, may have a broader target profile requiring further exploration."],["dc.identifier.doi","10.1042/BJ20061239"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86819"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1470-8728"],["dc.relation.issn","0264-6021"],["dc.title","An active site tyrosine residue is essential for amidohydrolase but not for esterase activity of a class 2 histone deacetylase-like bacterial enzyme"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","107"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","354"],["dc.contributor.author","Nielsen, Tine Kragh"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:53:41Z"],["dc.date.available","2017-09-07T11:53:41Z"],["dc.date.issued","2005"],["dc.description.abstract","Histone deacetylases (HDACs) are among the most promising targets in cancer therapy. However, structural information greatly enhancing the design of HDAC inhibitors as novel chemotherapeutics has not been available on class 2 HDACs so far. Here we present the structure of the bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) that reveals high sequential and functional homology to human class 2 HDACs. FB188 HDAH is capable to remove the acetyl moiety from acetylated histones. Several HDAC specific inhibitors, which have been shown to inhibit tumor activity in both pre-clinical models and in clinical trials, also inhibit FB188 HDAH. We have determined the crystal structure of FB188 HDAH at a resolution of 1.6 angstrom in complex with the reaction product acetate, as well as in complex with the inhibitors suberoylanilide hydroxamic acid (SAHA) and cyclopentyle-propionyle hydroxamic acid (CypX) at a resolution of 1.57 angstrom and 1.75 angstrom, respectively. FB188 HDAH exhibits the canonical fold of class 1 HDACs and contains a catalytic zinc ion. The highest structural diversity compared to class 1 enzymes is found in loop regions especially in the area around the entrance of the active site, indicating significant differences among the acetylated proteins binding to class I and 2 HDACs, respectively. (c) 2005 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.jmb.2005.09.065"],["dc.identifier.gro","3143786"],["dc.identifier.isi","000233310800008"],["dc.identifier.pmid","16242151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1338"],["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","0022-2836"],["dc.title","Crystal Structure of a Bacterial Class 2 Histone Deacetylase Homologue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]