1XAG

CRYSTAL STRUCTURE OF STAPHLYOCOCCUS AUREUS 3-DEHYDROQUINATE SYNTHASE (DHQS) IN COMPLEX WITH ZN2+, NAD+ AND CARBAPHOSPHONATE

Summary for 1XAG

• Entry DOI: 10.2210/pdb1xag/pdb
• Related: 1NR5 1NRX 1NUA 1NVA 1NVB 1NVD 1NVE 1NVF 1XAH 1XAI 1XAJ 1XAL
• Descriptor: 3-dehydroquinate synthase, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: shikimate pathway, aromatic amino acid biosynthesis, dhqs, sadhqs, closed form, form a, domain movement, cyclase, lyase
• Biological source: Staphylococcus aureus
• Cellular location: Cytoplasm (Probable): Q6GGU4
• Total number of polymer chains: 1
• Total formula weight: 41535.17

Authors

Nichols, C.E.,Ren, J.,Leslie, K.,Dhaliwal, B.,Lockyer, M.,Charles, I.,Hawkins, A.R.,Stammers, D.K. (deposition date: 2004-08-25, release date: 2005-03-01, Last modification date: 2023-08-23)

Primary citation

Nichols, C.E.,Ren, J.,Leslie, K.,Dhaliwal, B.,Lockyer, M.,Charles, I.,Hawkins, A.R.,Stammers, D.K.
Comparison of ligand induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases.
J.Mol.Biol., 343:533-546, 2004

PubMed Abstract: 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.

PubMed: 15465043
DOI: 10.1016/j.jmb.2004.08.039

Experimental method

X-RAY DIFFRACTION (2.45 Å)