Specificity of substrate recognition by type II dehydroquinases as revealed by binding of polyanions1

FEBS Letters

Noble, Lorna J²  Coggins, John R²  Chalk, Peter A¹  Evans, Lewis D.B²  Price, Nicholas C²  Roszak, Aleksander W²  Lapthorn, Adrian J³  Matthews, Jennifer L²  Robinson, David A² 

[1]GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK

[2]Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK

[3]Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK

关键词: Dehydroquinase;    3-Dehydroquinic acid;    Substrate recognition;    X-ray crystallography;    Phosphate;    Sulfate;    MTDHQase;    dehydroquinase from Mycobacterium tuberculosis;    SCDHQase;    dehydroquinase from Streptomyces coelicolor;    HPDHQase;    dehydroquinase from Helicobacter pylori;    TBDMSCl;    t-butyldimethylsilyl chloride;    4-DMAP;    4-dimethylaminopyridine;    DMF;    dimethylformamide;    PDC;    pyridinium dichromate;   

DOI  :  10.1016/S0014-5793(02)03346-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The interactions between the polyanionic ligands phosphate and sulphate and the type II dehydroquinases from Streptomyces coelicolor and Mycobacterium tuberculosis have been characterised using a combination of structural and kinetic methods. From both approaches, it is clear that interactions are more complex in the case of the latter enzyme. The data provide new insights into the differences between the two enzymes in terms of substrate recognition and catalytic efficiency and may also explain the relative potencies of rationally designed inhibitors. An improved route to the synthesis of the substrate 3-dehydroquinic acid (dehydroquinate) is described.

【 授权许可】

Unknown