St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

The AEROPATH project targeting Pseudomonas aeruginosa : crystallographic studies for assessment of potential targets in early-stage drug discovery

Thumbnail
View/Open
Moynieetal2013ActaCrystF_AEROPATH.pdf (1.583Mb)
Date
01/2013
Author
Moynie, Lucile
Schnell, Robert
McMahon, Stephen A.
Sandalova, Tatyana
Abdelli Boulkeroua, Wassila
Schmidberger, Jason W.
Alphey, Magnus
Cukier, Cyprian
Duthie, Fraser
Kopec, Jolanta
Liu, Huanting
Jacewicz, Agata
Hunter, William N.
Naismith, James H.
Schneider, Gunter
Keywords
Acid
Reductase
Macromolecular crystallography
Molecular replacement
System
VI secretion
Diffraction data
Mechanistic implications
Crystal-structure
Uroporphyrinogen-III synthase
QD Chemistry
Metadata
Show full item record
Abstract
Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns.
Citation
Moynie , L , Schnell , R , McMahon , S A , Sandalova , T , Abdelli Boulkeroua , W , Schmidberger , J W , Alphey , M , Cukier , C , Duthie , F , Kopec , J , Liu , H , Jacewicz , A , Hunter , W N , Naismith , J H & Schneider , G 2013 , ' The AEROPATH project targeting Pseudomonas aeruginosa : crystallographic studies for assessment of potential targets in early-stage drug discovery ' , Acta Crystallographica. Section F, Structural biology and crystallization communications , vol. 69 , no. 1 , pp. 25-34 . https://doi.org/10.1107/S1744309112044739
Publication
Acta Crystallographica. Section F, Structural biology and crystallization communications
Status
Peer reviewed
DOI
https://doi.org/10.1107/S1744309112044739
ISSN
1744-3091
Type
Journal article
Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. http://creativecommons.org/licenses/by/2.0/uk/legalcode
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/3352

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter