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, Pi 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/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 Ki 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.
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December 1999
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Research Article|
November 24 1999
Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase
Peter K. CHIANG;
Peter K. CHIANG
1
*Walter Reed Army Institute of Research, Washington, DC 20307-5100, U.S.A.
†National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, U.S.A.
1To whom correspondence should be addressed at Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100, U.S.A. (e-mail peter.chiang@na.amedd.army.mil).
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Margaret E. CHAMBERLIN;
Margaret E. CHAMBERLIN
†National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Diarmuid NICHOLSON;
Diarmuid NICHOLSON
‡Walter Reed Army Medical Center, Washington, DC, U.S.A.
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Sandrine SOUBES;
Sandrine SOUBES
§National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Xin-zhuan SU;
Xin-zhuan SU
§National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Gangadharan SUBRAMANIAN;
Gangadharan SUBRAMANIAN
§National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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David E. LANAR;
David E. LANAR
*Walter Reed Army Institute of Research, Washington, DC 20307-5100, U.S.A.
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Sean T. PRIGGE;
Sean T. PRIGGE
*Walter Reed Army Institute of Research, Washington, DC 20307-5100, U.S.A.
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John P. SCOVILL;
John P. SCOVILL
*Walter Reed Army Institute of Research, Washington, DC 20307-5100, U.S.A.
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Louis H. MILLER;
Louis H. MILLER
§National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Janice Y. CHOU
Janice Y. CHOU
†National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Publisher: Portland Press Ltd
Received:
June 10 1999
Revision Received:
August 02 1999
Accepted:
September 02 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (2): 571–576.
Article history
Received:
June 10 1999
Revision Received:
August 02 1999
Accepted:
September 02 1999
Citation
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; Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase. Biochem J 1 December 1999; 344 (2): 571–576. doi: https://doi.org/10.1042/bj3440571
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