40
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Structure of Staphylococcus aureus adenylo­succinate lyase (PurB) and assessment of its potential as a target for structure-based inhibitor discovery

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The 2.5 Å resolution structure of S. aureus adenylosuccinate lyase is reported and compared with those of orthologues to assess its potential as a template for early stage drug discovery. AMP and a putative assignment of oxalate, the latter an artefact possibly arising from an impurity in the PEG used for crystallization, occupy the active site.

          Abstract

          The medium-resolution structure of adenylosuccinate lyase (PurB) from the bacterial pathogen Staphylococcus aureus in complex with AMP is presented. Oxalate, which is likely to be an artifact of crystallization, has been modelled in the active site and occupies a position close to that where succinate is observed in orthologous structures. PurB catalyzes reactions that support the provision of purines and the control of AMP/fumarate levels. As such, the enzyme is predicted to be essential for the survival of S. aureus and to be a potential therapeutic target. Comparisons of this pathogen PurB with the enzyme from Escherichia coli are presented to allow discussion concerning the enzyme mechanism. Comparisons with human PurB suggest that the close similarity of the active sites would make it difficult to identify species-specific inhibitors for this enyme. However, there are differences in the way that the subunits are assembled into dimers. The distinct subunit–subunit interfaces may provide a potential area to target by exploiting the observation that creation of the enzyme active site is dependent on oligomerization.

          Related collections

          Author and article information

          Journal
          Acta Crystallogr D Biol Crystallogr
          Acta Cryst. D
          Acta Crystallographica Section D: Biological Crystallography
          International Union of Crystallography
          0907-4449
          1399-0047
          01 August 2010
          09 July 2010
          09 July 2010
          : 66
          : Pt 8 ( publisher-idID: d100800 )
          : 881-888
          Affiliations
          [a ]Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
          Author notes
          Correspondence e-mail: w.n.hunter@ 123456dundee.ac.uk
          Article
          mh5035 ABCRE6 S0907444910020081
          10.1107/S0907444910020081
          2917274
          20693687
          14d38548-ceeb-440c-a5a1-0d8e071f2470
          © Fyfe et al. 2010

          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.

          History
          : 08 March 2010
          : 27 May 2010
          Categories
          Research Papers

          Microscopy & Imaging
          adenylosuccinate lyase,amp,oxalate,purine biosynthesis,purine cycle
          Microscopy & Imaging
          adenylosuccinate lyase, amp, oxalate, purine biosynthesis, purine cycle

          Comments

          Comment on this article