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Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli.
Mol Biochem Parasitol. 2000 Oct; 110(2):283-91.MB

Abstract

The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. Three reactions are involved in methylenetetrahydrofolate recycling: Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). Malarial bifunctional DHFR-TS is a well-studied, important target of established drugs such as pyrimethamine and cycloguanil. In sharp contrast, malarial SHMT remains largely uncharacterized. In the present study, a Plasmodium falciparum SHMT coding region was characterized. It had 1603 bp including two introns near the 5'-end of the gene: one 118 bp intron immediately after the start methionine and a 159 bp intron after an additional 34 amino acids. The three exons together coded for a 442 amino acid protein with 38-47% identity to SHMT sequences from other species. Expression of malarial SHMT coding sequence (minus the introns) into glyA mutants of Escherichia coli relieved glycine auxotrophy and permitted direct assay of SHMT catalytic activity in bacterial cell lysates. This is the first SHMT cloned and expressed from a protozoan parasite. The molecular tools developed in this study will be useful for developing potential antimalarials directed at SHMT.

Authors+Show Affiliations

Department of Biology, The Catholic University of America, Washington DC 20064, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11071283

Citation

Alfadhli, S, and P K. Rathod. "Gene Organization of a Plasmodium Falciparum Serine Hydroxymethyltransferase and Its Functional Expression in Escherichia Coli." Molecular and Biochemical Parasitology, vol. 110, no. 2, 2000, pp. 283-91.
Alfadhli S, Rathod PK. Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli. Mol Biochem Parasitol. 2000;110(2):283-91.
Alfadhli, S., & Rathod, P. K. (2000). Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli. Molecular and Biochemical Parasitology, 110(2), 283-91.
Alfadhli S, Rathod PK. Gene Organization of a Plasmodium Falciparum Serine Hydroxymethyltransferase and Its Functional Expression in Escherichia Coli. Mol Biochem Parasitol. 2000;110(2):283-91. PubMed PMID: 11071283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli. AU - Alfadhli,S, AU - Rathod,P K, PY - 2000/11/9/pubmed PY - 2001/5/22/medline PY - 2000/11/9/entrez SP - 283 EP - 91 JF - Molecular and biochemical parasitology JO - Mol. Biochem. Parasitol. VL - 110 IS - 2 N2 - The global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. Three reactions are involved in methylenetetrahydrofolate recycling: Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). Malarial bifunctional DHFR-TS is a well-studied, important target of established drugs such as pyrimethamine and cycloguanil. In sharp contrast, malarial SHMT remains largely uncharacterized. In the present study, a Plasmodium falciparum SHMT coding region was characterized. It had 1603 bp including two introns near the 5'-end of the gene: one 118 bp intron immediately after the start methionine and a 159 bp intron after an additional 34 amino acids. The three exons together coded for a 442 amino acid protein with 38-47% identity to SHMT sequences from other species. Expression of malarial SHMT coding sequence (minus the introns) into glyA mutants of Escherichia coli relieved glycine auxotrophy and permitted direct assay of SHMT catalytic activity in bacterial cell lysates. This is the first SHMT cloned and expressed from a protozoan parasite. The molecular tools developed in this study will be useful for developing potential antimalarials directed at SHMT. SN - 0166-6851 UR - https://www.unboundmedicine.com/medline/citation/11071283/Gene_organization_of_a_Plasmodium_falciparum_serine_hydroxymethyltransferase_and_its_functional_expression_in_Escherichia_coli_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-6851(00)00282-6 DB - PRIME DP - Unbound Medicine ER -