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Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A potential antimalarial target.
Mol Biochem Parasitol. 2009 Nov; 168(1):63-73.MB

Abstract

Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme required for folate recycling and dTMP synthesis. A cDNA encoding Plasmodium falciparum (Pf) SHMT was expressed as a hexa-histidine tagged protein in Escherichia coli BL21-CodonPlus (DE3)-RIL. The protein was purified and the process yielded 3.6 mg protein/l cell culture. Recombinant His(6)-tagged PfSHMT exhibits a visible spectrum characteristic of pyridoxal-5'-phosphate enzyme and catalyzes the reversible conversion of l-serine and tetrahydrofolate (H(4)folate) to glycine and 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate). Steady-state kinetics study indicates that His(6)-tagged PfSHMT catalyzes the reaction by a ternary-complex mechanism. The sequence of substrate binding to the enzyme was also examined by glycine product inhibition. A striking property that is unique for His(6)-tagged PfSHMT is the ability to use D-serine as a substrate in the folate-dependent serine-glycine conversion. Kinetic data in combination with expression result support the proposal of SHMT reaction being a regulatory step for dTMP cycle. This finding suggests that PfSHMT can be a potential target for antimalarial chemotherapy.

Authors+Show Affiliations

Department of Biochemistry and Center for Excellence in Protein Structure & Function, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19591881

Citation

Maenpuen, Somchart, et al. "Characterization of Plasmodium Falciparum Serine hydroxymethyltransferase-A Potential Antimalarial Target." Molecular and Biochemical Parasitology, vol. 168, no. 1, 2009, pp. 63-73.
Maenpuen S, Sopitthummakhun K, Yuthavong Y, et al. Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A potential antimalarial target. Mol Biochem Parasitol. 2009;168(1):63-73.
Maenpuen, S., Sopitthummakhun, K., Yuthavong, Y., Chaiyen, P., & Leartsakulpanich, U. (2009). Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A potential antimalarial target. Molecular and Biochemical Parasitology, 168(1), 63-73. https://doi.org/10.1016/j.molbiopara.2009.06.010
Maenpuen S, et al. Characterization of Plasmodium Falciparum Serine hydroxymethyltransferase-A Potential Antimalarial Target. Mol Biochem Parasitol. 2009;168(1):63-73. PubMed PMID: 19591881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A potential antimalarial target. AU - Maenpuen,Somchart, AU - Sopitthummakhun,Kittipat, AU - Yuthavong,Yongyuth, AU - Chaiyen,Pimchai, AU - Leartsakulpanich,Ubolsree, Y1 - 2009/07/08/ PY - 2009/04/05/received PY - 2009/06/02/revised PY - 2009/06/25/accepted PY - 2009/7/14/entrez PY - 2009/7/14/pubmed PY - 2009/10/17/medline SP - 63 EP - 73 JF - Molecular and biochemical parasitology JO - Mol. Biochem. Parasitol. VL - 168 IS - 1 N2 - Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme required for folate recycling and dTMP synthesis. A cDNA encoding Plasmodium falciparum (Pf) SHMT was expressed as a hexa-histidine tagged protein in Escherichia coli BL21-CodonPlus (DE3)-RIL. The protein was purified and the process yielded 3.6 mg protein/l cell culture. Recombinant His(6)-tagged PfSHMT exhibits a visible spectrum characteristic of pyridoxal-5'-phosphate enzyme and catalyzes the reversible conversion of l-serine and tetrahydrofolate (H(4)folate) to glycine and 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate). Steady-state kinetics study indicates that His(6)-tagged PfSHMT catalyzes the reaction by a ternary-complex mechanism. The sequence of substrate binding to the enzyme was also examined by glycine product inhibition. A striking property that is unique for His(6)-tagged PfSHMT is the ability to use D-serine as a substrate in the folate-dependent serine-glycine conversion. Kinetic data in combination with expression result support the proposal of SHMT reaction being a regulatory step for dTMP cycle. This finding suggests that PfSHMT can be a potential target for antimalarial chemotherapy. SN - 1872-9428 UR - https://www.unboundmedicine.com/medline/citation/19591881/Characterization_of_Plasmodium_falciparum_serine_hydroxymethyltransferase_A_potential_antimalarial_target_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-6851(09)00183-2 DB - PRIME DP - Unbound Medicine ER -