title: Purification and properties of recombinant Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase.
abstract: Recombinant S-adenosyl-L-homocysteine (SAH) hydrolase of the malaria parasite Plasmodium falciparum was expressed in Escherichia coli, purified to homogeneity and characterized. Comparison of the malaria parasite SAH hydrolase with that derived from the human gene indicated marked differences in kcat values. The values of both forward and reverse reactions of P. falciparum SAH hydrolase are more than 21-fold smaller than those of the human enzyme. Km values of the parasite and human SAH enzymes are 1.2 and 7.8 microM, respectively. On the other hand, IC50 values of neplanocin A, a strong inhibitor of SAH hydrolase and a growth inhibitor of P. falciparum, are 101 nM for the parasite enzyme and 47 nM for human enzyme. P. falciparum SAH hydrolase has been thought to be a target for a chemotherapeutic agent against malaria. This study may make it possible to develop a specific inhibitor for the parasite SAH hydrolase.
authors.affiliation: Laboratory of Molecular Biochemistry, Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakanishi
authors.forename: A
authors.initials: A
authors.lastname: Iwata
authors.forename: C
authors.initials: C
authors.lastname: Yatome
authors.forename: Y
authors.initials: Y
authors.lastname: Kitade
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D043383:Adenosylhomocysteinase; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D007700:Kinetics; D008970:Molecular Weight; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D011930:Reaction Time; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013696:Temperature
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C031096:neplanocin A; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine