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","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","1116"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","1123"],["dc.bibliographiccitation.volume","324"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:49:26Z"],["dc.date.available","2021-06-01T10:49:26Z"],["dc.date.issued","2004"],["dc.identifier.doi","10.1016/j.bbrc.2004.09.155"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86291"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0006-291X"],["dc.title","Members of the histone deacetylase superfamily differ in substrate specificity towards small synthetic substrates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","138"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Molecular Genetics and Metabolism"],["dc.bibliographiccitation.lastpage","147"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Hildmann, Christian"],["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.2003.08.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86485"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","1096-7192"],["dc.title","Recent progress in the development of assays suited for histone deacetylase inhibitor screening"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2328"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Bacteriology"],["dc.bibliographiccitation.lastpage","2339"],["dc.bibliographiccitation.volume","186"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Ninkovic, Milena"],["dc.contributor.author","Dietrich, Rüdiger"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Zimmermann, Thomas"],["dc.contributor.author","Birch, Olwen M."],["dc.contributor.author","Bernegger, Christine"],["dc.contributor.author","Loidl, Peter"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:47:34Z"],["dc.date.available","2021-06-01T10:47:34Z"],["dc.date.issued","2004"],["dc.description.abstract","ABSTRACT The full-length gene encoding the histone deacetylase (HDAC)-like amidohydrolase (HDAH) from Bordetella or Alcaligenes ( Bordetella/Alcaligenes ) strain FB188 (DSM 11172) was cloned using degenerate primer PCR combined with inverse-PCR techniques and ultimately expressed in Escherichia coli . The expressed enzyme was biochemically characterized and found to be similar to the native enzyme for all properties examined. Nucleotide sequence analysis revealed an open reading frame of 1,110 bp which encodes a polypeptide with a theoretical molecular mass of 39 kDa. Interestingly, peptide sequencing disclosed that the N-terminal methionine is lacking in the mature wild-type enzyme, presumably due to the action of methionyl aminopeptidase. Sequence database searches suggest that the new amidohydrolase belongs to the HDAC superfamily, with the closest homologs being found in the subfamily assigned acetylpolyamine amidohydrolases (APAH). The APAH subfamily comprises enzymes or putative enzymes from such diverse microorganisms as Pseudomonas aeruginosa , Archaeoglobus fulgidus , and the actinomycete Mycoplana ramosa (formerly M. bullata ). The FB188 HDAH, however, is only moderately active in catalyzing the deacetylation of acetylpolyamines. In fact, FB188 HDAH exhibits significant activity in standard HDAC assays and is inhibited by known HDAC inhibitors such as trichostatin A and suberoylanilide hydroxamic acid (SAHA). Several lines of evidence indicate that the FB188 HDAH is very similar to class 1 and 2 HDACs and contains a Zn 2+ ion in the active site which contributes significantly to catalytic activity. Initial biotechnological applications demonstrated the extensive substrate spectrum and broad optimum pH range to be excellent criteria for using the new HDAH from Bordetella/Alcaligenes strain FB188 as a biocatalyst in technical biotransformations, e.g., within the scope of human immunodeficiency virus reverse transcriptase inhibitor synthesis."],["dc.identifier.doi","10.1128/JB.186.8.2328-2339.2004"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85648"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1098-5530"],["dc.relation.issn","0021-9193"],["dc.title","A New Amidohydrolase from Bordetella or Alcaligenes Strain FB188 with Similarities to Histone Deacetylases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]