{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"Structural studies to inform antimicrobial drug discovery and the basis of immunity against T6 effectors","abstract":"Work presented in this thesis is in two parts.<br/>Part one: The X-ray crystal structures of potential antimicrobial drug targets.<br/>The protein IspF (2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, EC: 4.6.1.12) from two pathogens (Burkholderia cenocepacia and Plasmodium falciparum) has been investigated. IspF is an enzyme of isoprenoid-precursor biosynthesis and is considered to be a potential drug target. The results of structural and fragment-screening efforts presented here inform early stage drug discovery efforts.<br/>The structure of the PabC protein (4-amino-4-deoxychorismate lyase, EC: 4.1.3.38) from the Gram-negative pathogen Pseudomonas aeruginosa was also determined. PabC is involved in the production of para-aminobenzoic acid on the path to folate. Comparisons with previously solved PabC structures identified a spatially conserved tyrosine residue in the active site and suggest that a re-evaluation of a published mechanism is warranted.<br/>Part two: Immunity proteins in the Gram-negative Type VI secretion system.<br/>The X-ray crystal structures of the proteins Rap1a and Rap2a from Serratia marcescens, inhibitors of the peptidoglycan amidase toxins secreted by some Gram-negative bacteria employing the Type VI secretion pathway, were determined by molecular replacement and analysed.","abstract_html":"Work presented in this thesis is in two parts.&lt;br/&gt;Part one: The X-ray crystal structures of potential antimicrobial drug targets.&lt;br/&gt;The protein IspF (2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, EC: 4.6.1.12) from two pathogens (Burkholderia cenocepacia and Plasmodium falciparum) has been investigated. IspF is an enzyme of isoprenoid-precursor biosynthesis and is considered to be a potential drug target. The results of structural and fragment-screening efforts presented here inform early stage drug discovery efforts.&lt;br/&gt;The structure of the PabC protein (4-amino-4-deoxychorismate lyase, EC: 4.1.3.38) from the Gram-negative pathogen Pseudomonas aeruginosa was also determined. PabC is involved in the production of para-aminobenzoic acid on the path to folate. Comparisons with previously solved PabC structures identified a spatially conserved tyrosine residue in the active site and suggest that a re-evaluation of a published mechanism is warranted.&lt;br/&gt;Part two: Immunity proteins in the Gram-negative Type VI secretion system.&lt;br/&gt;The X-ray crystal structures of the proteins Rap1a and Rap2a from Serratia marcescens, inhibitors of the peptidoglycan amidase toxins secreted by some Gram-negative bacteria employing the Type VI secretion pathway, were determined by molecular replacement and analysed.","abstract_has_math":false,"creators":["O'Rourke, Patrick"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Hunter, William"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-24T02:07:46Z","subjects":["X-ray","Crystallography","Structural biology","Drug discovery","Antimicrobial","Type VI secretion","IspF","PabC","2C-methyl-D-erythritol 2,4-cyclodiphosphate","Para-aminobenzoic acid","4-amino-4-deoxychorismate lyase","fragment screening"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hunter, William"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Biotechnology and Biological Sciences Research Council"]},{"key":"dc:creator","label":"Author","values":["O'Rourke, Patrick"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013"]},{"key":"dc:date.issued","label":"Date","values":["2013"]},{"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/f4b1cd50-c6b3-4cbb-b313-344106bfce5c"]},{"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":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["X-ray","Crystallography","Structural biology","Drug discovery","Antimicrobial","Type VI secretion","IspF","PabC","2C-methyl-D-erythritol 2,4-cyclodiphosphate","Para-aminobenzoic acid","4-amino-4-deoxychorismate lyase","fragment screening"]}]},{"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/f4b1cd50-c6b3-4cbb-b313-344106bfce5c","https://discovery.dundee.ac.uk/en/studentTheses/f4b1cd50-c6b3-4cbb-b313-344106bfce5c"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/3384819/O_Rourke_phd_2013.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Work presented in this thesis is in two parts.<br/>Part one: The X-ray crystal structures of potential antimicrobial drug targets.<br/>The protein IspF (2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, EC: 4.6.1.12) from two pathogens (Burkholderia cenocepacia and Plasmodium falciparum) has been investigated. IspF is an enzyme of isoprenoid-precursor biosynthesis and is considered to be a potential drug target. The results of structural and fragment-screening efforts presented here inform early stage drug discovery efforts.<br/>The structure of the PabC protein (4-amino-4-deoxychorismate lyase, EC: 4.1.3.38) from the Gram-negative pathogen Pseudomonas aeruginosa was also determined. PabC is involved in the production of para-aminobenzoic acid on the path to folate. Comparisons with previously solved PabC structures identified a spatially conserved tyrosine residue in the active site and suggest that a re-evaluation of a published mechanism is warranted.<br/>Part two: Immunity proteins in the Gram-negative Type VI secretion system.<br/>The X-ray crystal structures of the proteins Rap1a and Rap2a from Serratia marcescens, inhibitors of the peptidoglycan amidase toxins secreted by some Gram-negative bacteria employing the Type VI secretion pathway, were determined by molecular replacement and analysed."]},{"key":"dc:title","label":"Title","values":["Structural studies to inform antimicrobial drug discovery and the basis of immunity against T6 effectors"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hunter, William"],"dc:contributor.sponsor":["Biotechnology and Biological Sciences Research Council"],"dc:creator":["O'Rourke, Patrick"],"dc:date":["2013"],"dc:date.issued":["2013"],"dc:description.abstract":["Work presented in this thesis is in two parts.<br/>Part one: The X-ray crystal structures of potential antimicrobial drug targets.<br/>The protein IspF (2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, EC: 4.6.1.12) from two pathogens (Burkholderia cenocepacia and Plasmodium falciparum) has been investigated. IspF is an enzyme of isoprenoid-precursor biosynthesis and is considered to be a potential drug target. The results of structural and fragment-screening efforts presented here inform early stage drug discovery efforts.<br/>The structure of the PabC protein (4-amino-4-deoxychorismate lyase, EC: 4.1.3.38) from the Gram-negative pathogen Pseudomonas aeruginosa was also determined. PabC is involved in the production of para-aminobenzoic acid on the path to folate. 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