'''CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+ AND NAD+'''
===CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+ AND NAD+===
==Overview==
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Dehydroquinate synthase (DHQS) is a potential target for the development of novel broad-spectrum antimicrobial drugs, active against both prokaryotes and lower eukaryotes. Structures have been reported for Aspergillus nidulans DHQS (AnDHQS) in complexes with a range of ligands. Analysis of these AnDHQS structures showed that a large-scale domain movement occurs during the normal catalytic cycle, with a complex series of structural elements propagating substrate binding-induced conformational changes away from the active site to distal locations. Compared to corresponding fungal enzymes, DHQS from bacterial species are both mono-functional and significantly smaller. We have therefore determined the structure of Staphylococcus aureus DHQS (SaDHQS) in five liganded states, allowing comparison of ligand-induced conformational changes and mechanisms of domain closure between fungal and bacterial enzymes. This comparative analysis shows that substrate binding initiates a large-scale domain closure in both species' DHQS and that the active site stereochemistry, of the catalytically competent closed-form enzyme thus produced, is also highly conserved. However, comparison of AnDHQS and SaDHQS open-form structures, and analysis of the putative dynamic processes by which the transition to the closed-form states are made, shows a far lower degree of similarity, indicating a significant structural divergence. As a result, both the nature of the propagation of conformational change and the mechanical systems involved in this propagation are quite different between the DHQSs from the two species.
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==About this Structure==
==About this Structure==
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[[Category: Sadhq]]
[[Category: Sadhq]]
[[Category: Shikimate pathway]]
[[Category: Shikimate pathway]]
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Revision as of 14:15, 27 July 2008
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CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+ AND NAD+CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+ AND NAD+
Comparison of ligand-induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases., Nichols CE, Ren J, Leslie K, Dhaliwal B, Lockyer M, Charles I, Hawkins AR, Stammers DK, J Mol Biol. 2004 Oct 22;343(3):533-46. PMID:15465043
