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Determination of the DNA and amino acid sequences of the lactate dehydrogenase gene from Plasmodium falciparum strains K1 and PF-FCBR: A route to the design of new antimalarials

This paper describes cloning of the gene coding for the lactate dehydrogenase (LDH) gene from the two different strains of Plasmodium falciparum, K1 and PF FCBR. The DNA sequences of LDH genes of these two strains were found to be identical. | Turk J Biol 25 (2001) 241-250 © TÜB‹TAK Determination of the DNA and Amino Acid Sequences of the Lactate Dehydrogenase Gene from Plasmodium falciparum Strains K1 and PF FCBR: A Route to the Design of New Antimalarials Dilek TURGUT BALIK University of F›rat Faculty of Arts and Sciences Department of Biology Elaz›¤ - TURKEY J. John HOLBROOK Molecular Recognition Centre and Department of Biochemistry, University of Bristol School of Medical Sciences, Bristol BS8 1TD, U.K. Received: 19.11.1999 Abstract : This paper describes cloning of the gene coding for the lactate dehydrogenase (LDH) gene from the two different strains of Plasmodium falciparum, K1 and PF FCBR. The DNA sequences of LDH genes of these two strains were found to be identical. Amino acid sequence alignment of LDH from P. falciparum strains K1 and PF FCBR (PfLDH) to some other known LDH sequences showed that PfLDH has 29% residue identities with Bacillus stearothermophilus (BsLDH) and 29%, 31%, 33% with dogfish, man-M4, and pig-M4 LDHs, respectively. It was also shown that PfLDH has insertions and single amino acid deletions. Two deletions are glutamate-48 and glycine-217. It has a single amino acid insertion, a tyrosine, between residues 73 and 74, and most remarkably a five residue insertion in the catalytic loop compared to other LDH sequences. This five residue insertion could be exploited in drug design. Key Words: lactate dehydrogenase / antimalarials / DNA sequencing / gene cloning / catalytic loop Plasmodium falciparum soylar› K1 and PF FCBR’›n Laktat Dehidrogenaz Geninin DNA ve Aminoasit Dizilerinin Belirlenmesi: Yeni Antimalariallar›n Tasar›m›na Bir Yol Özet : Bu makalede laktat dehidrogenaz (LDH) geninin Plasmodium falciparum'un iki farkl› soyu olan K1 ve PF FCBR'dan klonlanmas› tan›mlanmaktad›r. Bu iki soyun nükleotid dizilerinin tümüyle biribirinin ayn› oldu¤u bulunmufltur. P. falciparum soylar› K1 ve PF FCBR'›n LDH’lerinin (PfLDH) amino asit dizilerinin, amino asit dizileri bilinen di¤er