Abstract |
The gene coding for myristoyl-CoA:protein N-myristoyltransferase (NMT) has been cloned from the malaria parasite Plasmodium falciparum. The gene appears to be single copy and mRNA is expressed in asexual blood-stage forms. Comparison of cDNA and genomic sequences identified three small introns. The open reading frame codes for a 410-amino-acid protein and no evidence of forms with an extended N-terminal coding sequence was obtained. Residues important in substrate binding and in the catalytic mechanism in other species are conserved. The protein was expressed from a plasmid in Escherichia coli, partially purified and shown to have enzymic activity using a synthetic peptide substrate. Comparison of the malaria parasite protein with that derived from the human gene showed a different pattern of inhibition by chemical modification. Human NMT activity was inhibited by diethylpyrocarbonate and partially inhibited by iodacetamide, whereas P. falciparum NMT activity was not inhibited by either pre-treatment. Since the enzyme in infectious fungi is a target for potential chemotherapeutic drugs, it should also be investigated in the context of parasitic infections such as that responsible for malaria.
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Authors | R S Gunaratne, M Sajid, I T Ling, R Tripathi, J A Pachebat, A A Holder |
Journal | The Biochemical journal
(Biochem J)
Vol. 348 Pt 2
Pg. 459-63
(Jun 01 2000)
ISSN: 0264-6021 [Print] England |
PMID | 10816442
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Recombinant Proteins
- Acyltransferases
- glycylpeptide N-tetradecanoyltransferase
- Diethyl Pyrocarbonate
- Ethylmaleimide
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Topics |
- Acyltransferases
(genetics, isolation & purification, metabolism)
- Amino Acid Sequence
- Animals
- Candida albicans
(enzymology)
- Cloning, Molecular
- Diethyl Pyrocarbonate
(pharmacology)
- Ethylmaleimide
(pharmacology)
- Humans
- Kinetics
- Molecular Sequence Data
- Open Reading Frames
- Plasmodium falciparum
(enzymology)
- Polymerase Chain Reaction
- Protein Biosynthesis
- Recombinant Proteins
(metabolism)
- Saccharomyces cerevisiae
(enzymology)
- Sequence Alignment
- Sequence Homology, Amino Acid
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