Roszak, A.W. and Robinson, D.A. and Krell, T. and Hunter, I.S. and Fredrickson, M. and Abell, C. and Coggins, J.R. and Lapthorn, A.J. (2002) The structure and mechanism of the type II dehydroquinase from streptomyces coelicolor. Structure, 10 (4). pp. 493-503. ISSN 0969-2126Full text not available in this repository. (Request a copy from the Strathclyde author)
The structure of the type II DHQase from Streptomyces coelicolor has been solved and refined to high resolution in complexes with a number of ligands, including dehydroshikimate and a rationally designed transition state analogue, 2,3-anhydro-quinic acid. These structures define the active site of the enzyme and the role of key amino acid residues and provide snap shots of the catalytic cycle. The resolution of the flexible lid domain (residues 21–31) shows that the invariant residues Arg23 and Tyr28 close over the active site cleft. The tyrosine acts as the base in the initial proton abstraction, and evidence is provided that the reaction proceeds via an enol intermediate. The active site of the structure of DHQase in complex with the transition state analog also includes molecules of tartrate and glycerol, which provide a basis for further inhibitor design.
|Keywords:||shikimate pathway, rational drug design , enzyme mechanism, X-ray structure, transition state analog , dehydroquinase, Pharmacy and materia medica|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||27 Mar 2012 09:16|
|Last modified:||22 Mar 2017 09:58|