{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"Structural studies of paired PHD finger-bromodomain chromatin-binding modules: targeting epigenetic readers with chemical probes","abstract":"The use of chemical probes is a powerful tool that can help to address important biological questions.
The study presented in this thesis aims to target reader domains of chromatin-associated proteins with small molecules, in order to provide information on their ligandability, useful to develop - potent chemical probes. This thesis work is divided in three parts.
In the first and second part it is shown how structural information obtained by the use of synthetic peptides to study the binding mode of reader domains with their natural binding partner can be combined with fragment screening to gauge future optimization of small molecules. The first section described the disclosure of the binding mode of the H3 histone tail by the PHD zinc finger of BAZ2A. A crystal structure of the complex of BAZ2A with the H3 10-mer peptide identified a helical conformation of H3 upon binding with the PHD. This information coupled with further structural and biophysical analysis led to the identification of a subfamily of PHD characterized by an acidic patch on the helical turn, which is responsible of inducing helicity on H3 tail upon binding.
The second part of the work investigated the ligandability of the PHD zinc finger domains of BAZ2A and BAZ2B. Using a combination of biophysical techniques and X-ray crystallography it was probed that it is possible to target these reader domains. Despite the similarities of the two PHDs, comparison of the fragment-bound crystal structures of the two proteins highlighted some differences in the binding mode.
The last part of the project describes the several attempts performed in trying to elucidate the histone binding partner of the PHD-BrD tandem of the chromatin-related proteins BAZ1B and TRIM66, both involved in diseases.","abstract_html":"The use of chemical probes is a powerful tool that can help to address important biological questions.<br/><br/>The study presented in this thesis aims to target reader domains of chromatin-associated proteins with small molecules, in order to provide information on their ligandability, useful to develop - potent chemical probes. This thesis work is divided in three parts.<br/><br/>In the first and second part it is shown how structural information obtained by the use of synthetic peptides to study the binding mode of reader domains with their natural binding partner can be combined with fragment screening to gauge future optimization of small molecules. The first section described the disclosure of the binding mode of the H3 histone tail by the PHD zinc finger of BAZ2A. A crystal structure of the complex of BAZ2A with the H3 10-mer peptide identified a helical conformation of H3 upon binding with the PHD. This information coupled with further structural and biophysical analysis led to the identification of a subfamily of PHD characterized by an acidic patch on the helical turn, which is responsible of inducing helicity on H3 tail upon binding.<br/><br/>The second part of the work investigated the ligandability of the PHD zinc finger domains of BAZ2A and BAZ2B. Using a combination of biophysical techniques and X-ray crystallography it was probed that it is possible to target these reader domains. Despite the similarities of the two PHDs, comparison of the fragment-bound crystal structures of the two proteins highlighted some differences in the binding mode.<br/><br/>The last part of the project describes the several attempts performed in trying to elucidate the histone binding partner of the PHD-BrD tandem of the chromatin-related proteins BAZ1B and TRIM66, both involved in diseases.","abstract_has_math":false,"creators":["Amato, Anastasia"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Ciulli, Alessio"],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-24T02:08:32Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ciulli, Alessio"]},{"key":"dc:creator","label":"Author","values":["Amato, Anastasia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018"]},{"key":"dc:date.issued","label":"Date","values":["2018"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Biological Chemistry and Drug Discovery"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b","https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/19981927/AACorrected_FinalThesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The use of chemical probes is a powerful tool that can help to address important biological questions.
The study presented in this thesis aims to target reader domains of chromatin-associated proteins with small molecules, in order to provide information on their ligandability, useful to develop - potent chemical probes. This thesis work is divided in three parts.
In the first and second part it is shown how structural information obtained by the use of synthetic peptides to study the binding mode of reader domains with their natural binding partner can be combined with fragment screening to gauge future optimization of small molecules. The first section described the disclosure of the binding mode of the H3 histone tail by the PHD zinc finger of BAZ2A. A crystal structure of the complex of BAZ2A with the H3 10-mer peptide identified a helical conformation of H3 upon binding with the PHD. This information coupled with further structural and biophysical analysis led to the identification of a subfamily of PHD characterized by an acidic patch on the helical turn, which is responsible of inducing helicity on H3 tail upon binding.
The second part of the work investigated the ligandability of the PHD zinc finger domains of BAZ2A and BAZ2B. Using a combination of biophysical techniques and X-ray crystallography it was probed that it is possible to target these reader domains. Despite the similarities of the two PHDs, comparison of the fragment-bound crystal structures of the two proteins highlighted some differences in the binding mode.
The last part of the project describes the several attempts performed in trying to elucidate the histone binding partner of the PHD-BrD tandem of the chromatin-related proteins BAZ1B and TRIM66, both involved in diseases."]},{"key":"dc:title","label":"Title","values":["Structural studies of paired PHD finger-bromodomain chromatin-binding modules: targeting epigenetic readers with chemical probes"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ciulli, Alessio"],"dc:creator":["Amato, Anastasia"],"dc:date":["2018"],"dc:date.issued":["2018"],"dc:description.abstract":["The use of chemical probes is a powerful tool that can help to address important biological questions.
The study presented in this thesis aims to target reader domains of chromatin-associated proteins with small molecules, in order to provide information on their ligandability, useful to develop - potent chemical probes. This thesis work is divided in three parts.
In the first and second part it is shown how structural information obtained by the use of synthetic peptides to study the binding mode of reader domains with their natural binding partner can be combined with fragment screening to gauge future optimization of small molecules. The first section described the disclosure of the binding mode of the H3 histone tail by the PHD zinc finger of BAZ2A. A crystal structure of the complex of BAZ2A with the H3 10-mer peptide identified a helical conformation of H3 upon binding with the PHD. This information coupled with further structural and biophysical analysis led to the identification of a subfamily of PHD characterized by an acidic patch on the helical turn, which is responsible of inducing helicity on H3 tail upon binding.
The second part of the work investigated the ligandability of the PHD zinc finger domains of BAZ2A and BAZ2B. Using a combination of biophysical techniques and X-ray crystallography it was probed that it is possible to target these reader domains. Despite the similarities of the two PHDs, comparison of the fragment-bound crystal structures of the two proteins highlighted some differences in the binding mode.
The last part of the project describes the several attempts performed in trying to elucidate the histone binding partner of the PHD-BrD tandem of the chromatin-related proteins BAZ1B and TRIM66, both involved in diseases."],"dc:identifier":["oai:discovery.dundee.ac.uk:studenttheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b","https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"],"dc:identifier.uri":["https://discovery.dundee.ac.uk/files/19981927/AACorrected_FinalThesis.pdf"],"dc:language":["eng"],"dc:publisher.department":["Biological Chemistry and Drug Discovery"],"dc:publisher.institution":["University of Dundee"],"dc:relation.isreferencedby":["https://discovery.dundee.ac.uk/en/studentTheses/f8c8d2fe-5082-403f-8e73-098d8a713b2b"],"dc:title":["Structural studies of paired PHD finger-bromodomain chromatin-binding modules: targeting epigenetic readers with chemical probes"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:08:32Z"}