Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase

S-Adenosylmethionine (AdoMet) synthetase (SAMS: EC 2.5.1.6) catalyses the formation of AdoMet from methionine and ATP. We have cloned a gene for Plasmodium falciparum AdoMet synthetase (PfSAMS) (GenBank accession no. AF097923), consisting of 1209 base pairs with no introns. The gene encodes a polype...

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Bibliographic Details
Published in:Biochemical journal 1999-12, Vol.344 Pt 2 (2), p.571-576
Main Authors: Chiang, P K, Chamberlin, M E, Nicholson, D, Soubes, S, Su, X, Subramanian, G, Lanar, D E, Prigge, S T, Scovill, J P, Miller, L H, Chou, J Y
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Composition
Catalytic Domain
Chromosome Mapping
Cloning, Molecular
Cycloleucine - pharmacology
DNA, Complementary - genetics
Evolution, Molecular
Gene Dosage
Genes, Protozoan
Humans
Liver - enzymology
Methionine Adenosyltransferase - antagonists & inhibitors
Methionine Adenosyltransferase - classification
Methionine Adenosyltransferase - genetics
Methionine Adenosyltransferase - metabolism
Models, Molecular
Molecular Sequence Data
Phylogeny
Plasmodium falciparum - enzymology
Sequence Homology, Amino Acid
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Summary:S-Adenosylmethionine (AdoMet) synthetase (SAMS: EC 2.5.1.6) catalyses the formation of AdoMet from methionine and ATP. We have cloned a gene for Plasmodium falciparum AdoMet synthetase (PfSAMS) (GenBank accession no. AF097923), consisting of 1209 base pairs with no introns. The gene encodes a polypeptide (PfSAMS) of 402 amino acids with a molecular mass of 44844 Da, and has an overall base composition of 67% A+T. PfSAMS is probably a single copy gene, and was mapped to chromosome 9. The PfSAMS protein is highly homologous to all other SAMS, including a conserved motif for the phosphate-binding P-loop, HGGGAFSGKD, and the signature hexapeptide, GAGDQG. All the active-site amino acids for the binding of ADP, P(i) and metal ions are similarly preserved, matching entirely those of human hepatic SAMS and Escherichia coli SAMS. Molecular modelling of PfSAMS guided by the X-ray crystal structure of E. coli SAMS indicates that PfSAMS binds ATP/Mg(2+) in a manner similar to that seen in the E. coli SAMS structure. However, the PfSAMS model shows that it can not form tetramers as does E. coli SAMS, and is probably a dimer instead. There was a differential sensitivity towards the inhibition by cycloleucine between the expressed PfSAMS and the human hepatic SAMS with K(i) values of 17 and 10 mM, respectively. Based on phylogenetic analysis using protein parsimony and neighbour-joining algorithms, the malarial PfSAMS is closely related to SAMS of other protozoans and plants.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3440571