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Localization and nucleotide specificity of Blastocystis succinyl-CoA synthetase.| Authors: | Karleigh Hamblin, Daron M Standley, Matthew B Rogers, Alexandra Stechmann, Andrew J Roger, Robin Maytum, Mark van der Giezen | | Language: | Eng. | | Date: | 23-05-2008 | | Journal: | Molecular microbiology
(1365-2958)
| | Release: | Mol Microbiol. 2008 Jun;68(6):1395-405 | |
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Abstract:
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The anaerobic lifestyle of the intestinal parasite Blastocystis raises questions about the biochemistry and function of its mitochondria-like organelles. We have characterized the Blastocystis succinyl-CoA synthetase (SCS), a tricarboxylic acid cycle enzyme that conserves energy by substrate-level phosphorylation. We show that SCS localizes to the enigmatic Blastocystis organelles, indicating that these organelles might play a similar role in energy metabolism as classic mitochondria. Although analysis of residues inside the nucleotide-binding site suggests that Blastocystis SCS is GTP-specific, we demonstrate that it is ATP-specific. Homology modelling, followed by flexible docking and molecular dynamics simulations, indicates that while both ATP and GTP fit into the Blastocystis SCS active site, GTP is destabilized by electrostatic dipole interactions with Lys 42 and Lys 110, the side-chains of which lie outside the nucleotide-binding cavity. It has been proposed that residues in direct contact with the substrate determine nucleotide specificity in SCS. However, our results indicate that, in Blastocystis, an electrostatic gatekeeper controls which ligands can enter the binding site.
| | Copyright: | Molecular microbiology
School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK. | | Full text: |  EBSCO - HTML (needs subscription) | | |
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