Dehydroquinase type

Inhibition of Dehydroquinase Type II Dehydroquinase type II is an important enzyme in the shikimic and quinic routes. It ensures the reversible conversion of 3-dehydroquinate (DHQ) into 3-dehydroshrkimate (DHS). Ehmination of the hydroxyl is assisted by an acid/base catalysis that is associated with a residue of the active site. 

Stewart KA, Robinson DA, Lapthom AJ (2008) Type II dehydroquinase molecular replacement with many copies. Acta Crystallogr, D-Biol Crystallogr 64 108-118... 

M. Frederickson, J. R. Coggin, and C. Abell, Vinyl fluoride as an isoelectronic replacement for an enolate anion Inhibition of type II dehydroquinases, Chem. Commun., (2002) 1886-1887. 

The dehydration of 3-dehydroquinate to 3-dehydroshiki-mate catalyzed by 3-dehydroquinase (EC 4.2.1.10) is common to two metabolic pathways, the inicrobial biosynthetic shikimate pathway and the catabolic quinate pathway. This reaction is catalyzed by two completely different enzymes either a Type I enzyme that catalyzes a syn elimination or a Type II enzyme that catalyzes an anti elimination. 

The Type II 3-dehydroquinase is made up of 12 identical 16.5 kDa subunits of approximately 150 amino acid residues, which are arranged as a tetramer of trimers. The protein adopts a flavodoxin-like fold (i.e., belongs to the a/p class of proteins), with a parallel five-stranded P-sheet flanked on both sides by a-helices (Fig. 3a). The active site is located at the carboxyl end of the P-strands as in other a/p proteins, in the crevice produced by the specific topology of the P-sheet. " The loops from the P-strands 1 and 2 connect to helices in one direction, while those of P-strands 3, 4. and 5 connect to helices on the opposite face of the P-sheet. Between Strands 1 and 3, a crevice is formed, and this is where the active site is located (at least partially) in all a/p proteins. It should be noted that locating the active site of an enzyme is not as straightforward in the other classes of protein folds shown in Fig. 1. 

In the first crystal structure obtained for a Type II 3-dehydroquinase, Arg 21 and Tyr 28 were disordered... 

Fig. 3 Type 11 dehydroquinase a) a ribbon representation of the quaternary structure of the enzyme, with each peptide chain depicted in a different color. The inhibitor 2,3-anhydro-quinic acid is shown in space-filling representation, with atoms colored according to atom type, b) On the left is a detailed view of the enzyme active site as seen in the crystal structure, with the ligand highlighted in green and key amino acid residues labeled. This is compared with the traditional two-dimensional representation of the two steps of the enzyme mechanism on the right. (View this an in color at WWW.dekker.com.)...

Krell. T. Horsburgh, M.J. Cooper. A., et al. Localization of the active site of type II dehydroquinases. Identification of a common arginine-containing motif in the two classes of dehydroquinases. J. Biol. Chem. 1996. 271. 24492-24497. 

Bottomley. J.R. Hawkins, A.R. Kleanthous. C. Conformational ehanges and the role of metals in the meehanism of type n dehydroquinase from Aspergillus nidulans. Biochem. J. 1996, 319. 269-278. 

Harris. J.M. Gonzalez-Bello, C. Kleanthous. C.. et al. Evidence from kinetic isotope studies for an enolate intermediate in the mechanism of type II dehydroquinases. Biochem. J. 1996. 319. 333-336. 

Evidence (NMR) has been presented that a type (II) dehydroquinase transforms 3-dehydroquinate to 3-dehydroshikimate with anti-stereochemistry. ... 

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