1xaj

[[Image:1xaj.gif|left|200px]]

|PDB= 1xaj |SIZE=350|CAPTION= <scene name='initialview01'>1xaj</scene>, resolution 2.35&Aring;

|SITE=

|LIGAND= <scene name='pdbligand=CRB:[1R-(1ALPHA,3BETA,4ALPHA,5BETA)]-5-(PHOSPHONOMETHYL)-1,3,4-TRIHYDROXYCYCLOHEXANE-1-CARBOXYLIC+ACID'>CRB</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>

|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3-dehydroquinate_synthase 3-dehydroquinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.4 4.2.3.4] </span>

|GENE= aroB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 Staphylococcus aureus])

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xaj OCA], [http://www.ebi.ac.uk/pdbsum/1xaj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xaj RCSB]</span>

 

 

 

==Overview==

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.

 

==About this Structure==

1XAJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XAJ OCA].

 

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:[http://www.ncbi.nlm.nih.gov/pubmed/15465043 15465043]

[[Category: 3-dehydroquinate synthase]]

[[Category: Single protein]]

[[Category: Charles, I.]]

[[Category: Dhaliwal, B.]]

[[Category: Hawkins, A R.]]

[[Category: Leslie, K.]]

[[Category: Lockyer, M.]]

[[Category: Nichols, C E.]]

[[Category: Ren, J.]]

[[Category: Stammers, D K.]]