Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution.
The crystal structures of Salmonella typhimurium 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase (HMPP kinase) and its complex with substrate HMP have been determined. HMPP kinase catalyzes two separate ATP-dependent phosphorylation reactions and is an essential enzyme in the thiamin biosynthetic pathway. HMPP kinase is a homodimer with one active site per monomer and is structurally homologous to members of the ribokinase family. A comparison of the structure of HMPP kinase with other members of the ribokinase family suggests an evolutionary progression. Modeling studies suggest that HMPP kinase catalyzes both of its phosphorylation reactions using in-line displacement mechanisms. We propose that the active site accommodates the two separate reactions by providing two different binding modes for the phosphate group of HMP phosphate.
Cheng
Gong
G
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Bennett
Eric M
EM
Begley
Tadhg P
TP
Ealick
Steven E
SE
D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D008958:Models, Molecular; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry; D011487:Protein Conformation; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology*; D013379:Substrate Specificity
C101901:4-amino-5-hydroxymethyl-2-methylpyrimidine; D011743:Pyrimidines; C054356:bacimethrin; D017853:Phosphotransferases (Alcohol Group Acceptor); C022534:ribokinase; C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase