Source:http://linkedlifedata.com/resource/pubmed/id/10713131
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2000-4-12
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| pubmed:databankReference | |
| pubmed:abstractText |
The polyamines putrescine, spermidine, and spermine are crucial for cell differentiation and proliferation. Interference with polyamine biosynthesis by inhibition of the rate-limiting enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) has been discussed as a potential chemotherapy of cancer and parasitic infections. Usually both enzymes are individually transcribed and highly regulated as monofunctional proteins. We have isolated a cDNA from the malaria parasite Plasmodium falciparum that encodes both proteins on a single open reading frame, with the AdoMetDC domain in the N-terminal region connected to a C-terminal ODC domain by a hinge region. The predicted molecular mass of the entire transcript is 166 kDa. The ODC/AdoMetDC coding region was subcloned into the expression vector pASK IBA3 and transformed into the AdoMetDC- and ODC-deficient Escherichia coli cell line EWH331. The resulting recombinant protein exhibited both AdoMetDC and ODC activity and co-eluted after gel filtration on Superdex S-200 at approximately 333 kDa, which is in good agreement with the molecular mass of approximately 326 kDa determined for the native protein from isolated P. falciparum. SDS-polyacrylamide gel electrophoresis analysis of the recombinant ODC/AdoMetDC revealed a heterotetrameric structure of the active enzyme indicating processing of the AdoMetDC domain. The data presented describe the occurrence of a unique bifunctional ODC/AdoMetDC in P. falciparum, an organization which is possibly exploitable for the design of new antimalarial drugs.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosylmethionine Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Ornithine Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Protozoan,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
17
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| pubmed:volume |
275
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8097-102
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10713131-Adenosylmethionine Decarboxylase,
pubmed-meshheading:10713131-Amino Acid Sequence,
pubmed-meshheading:10713131-Animals,
pubmed-meshheading:10713131-Erythrocytes,
pubmed-meshheading:10713131-Gene Expression,
pubmed-meshheading:10713131-Gene Library,
pubmed-meshheading:10713131-Molecular Sequence Data,
pubmed-meshheading:10713131-Molecular Weight,
pubmed-meshheading:10713131-Multienzyme Complexes,
pubmed-meshheading:10713131-Open Reading Frames,
pubmed-meshheading:10713131-Ornithine Decarboxylase,
pubmed-meshheading:10713131-Plasmodium falciparum,
pubmed-meshheading:10713131-Polyamines,
pubmed-meshheading:10713131-RNA, Messenger,
pubmed-meshheading:10713131-RNA, Protozoan,
pubmed-meshheading:10713131-Recombinant Proteins,
pubmed-meshheading:10713131-Sequence Analysis, DNA,
pubmed-meshheading:10713131-Sequence Homology, Amino Acid
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| pubmed:year |
2000
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| pubmed:articleTitle |
In the human malaria parasite Plasmodium falciparum, polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase.
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| pubmed:affiliation |
Bernhard Nocht Institute for Tropical Medicine, Biochemical Parasitology, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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