Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase

Peter K. Chiang, Margaret E. Chamberlin, Diarmuid Nicholson, Sandrine Soubes, Xin Zhuan Su, Gangadharan Subramanian, David E. Lanar, Sean T. Prigge, John P. Scovill, Louis H. Miller, Janice Y. Chou

Research output: Contribution to journalArticlepeer-review

Abstract

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 44,844 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 Xray crystal structure of E. coli SAMS indicates that PfSAMS binds ATP/Mg2+ 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 K1 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.

Original languageEnglish (US)
Pages (from-to)571-576
Number of pages6
JournalBiochemical Journal
Volume344
Issue number2
DOIs
StatePublished - Dec 1 1999

Keywords

  • Chromosome
  • Cycloleucine
  • Modelling
  • Phylogeny

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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