Thiamine phosphate synthetase

AutoDock4 and Dock6 used with a homology model of thiamin phosphate synthetase NCI diversity set II docked in homology model. 39 compounds tested, 25 showed activity, and seven have >20% inhibition at 100 pg/mL. One compound also had an MIC99 of 6 pg/mL Khare et al. (89)... 

The hypE proteins are 302-376 residues long and appear to consist of three domains. Domain 1 shows sequence identity to a domain from phosphoribosyl-aminoimida-zole synthetase which is involved in the fifth step in de novo purine biosynthesis and to a domain in thiamine phosphate kinase which is involved in the synthesis of the cofactor thiamine diphosphate (TDP). TDP is required by enzymes which cleave the bond adjacent to carbonyl groups, e.g. phosphoketolase, transketolase or pyruvate decarboxylase. Domain 2 also shows identity to a domain found in thiamine phosphate kinase. Domain 3 appears to be unique to the HypF proteins. 

---