THE CRYSTAL STRUCTURE OF A TYPE II DEHYDROQUINASE FROM MYCOBACTERIUM TUBERCULOSIS. D.G.Gourley,¹ J.R.Coggins¹, A.R. Hawkins², and N.W. Isaacs¹. ¹Departments of Biochemistry and Chemistry University of Glasgow, Glasgow G128QQ,UK; ²Department of Biochemistry and Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH,UK.

Dehydroquinases (DHQases) are enzymes that catalyse the reversible dehydration of 3-dehydroquinate to 3-dehydroshikimate. The DHQase reaction is a common step in two important pathways: the shikimate pathway for aromatic biosynthesis and the catabolic pathway for quinate metabolism. Some of the aromatic compounds made by the shikimate pathway are essential to these organisms and thus contains viable targets for the design of anti-microbial drugs and herbicides. Two classes of DHQase exist with different biochemical and biophysical properties. The Type I DHQase is found in the shikimate pathways of plants, fungi and most bacteria but has never been found in the catabolic pathway. Type II DHQase has been found in the catabolic pathway and in the shikimate pathway of four organisms including Mycobacterium tuberculosis.

Crystals of type II DHQase from Mycobacterium tuberculosis belong to spacegroup F23 with a=b=c=127.8 and diffract to 1.9 Å resolution. The structure has been determined to 2.9 Å with MIR phases calculated from two derivatives followed by density modification. The fold has been identified as a/b type and is similar to the fold found in P-loop containing nucleotide triphosphate hydrolases such as p21^ras (Pai et al., Nature 341, 209-214).