Wynik wyszukiwania w bazie Polska Bibliografia Lekarska GBL
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FERDIG
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Tytuł oryginału:
Angiogenesis inhibitors specific for methionine aminopeptidase 2 as drugs for malaria and Leishmaniasis.
Autorzy:
Zhang
Peng,
Nicholson
Diarmuid E.,
Bujnicki
Janusz M.,
Su
Xinzhuan,
Brendle
James J.,
Ferdig
Michael,
Kyle
Dennis E.,
Milhous
Wilbur K.,
Chiang
Peter K.
Źródło:
J. Biomed. Sci. 2002: 9 (1) s.34-40, il., tab., bibliogr. 27 poz.
Sygnatura GBL:
313,488
Hasła klasyfikacyjne GBL:
mikrobiologia
farmacja
Typ dokumentu:
praca doświadczalna
praca opublikowana za granicą
tytuł obcojęzyczny
Wskaźnik treści:
in vitro
Streszczenie angielskie:
Methionine aminopeptidase 2(MetAP2) is responsible for the hydrolysis of the initiator methionine molecule from the majority of newly synthesized proteins. We have cloned the MetAP2 gene from the malaria parasite Plasmodium falciparum (PfMetAP2; GenBank accession number AF348320). The cloned PfMetAP2 has no intron, consists of 1,544 bp and encodes a protein of 354 amino acids with a molecular mass of 40,537 D and an overall base composition of 72.54 p.c. A + T. PfMetAP2 has 40 p.c. sequence identity with human MetAP2 and 45 p.c. identity with yeast MetAP2, and is located in chromosome 14 of P. falciparum. The three-dimensional structure of PfMetAP2 has been modeled based on the crystal structure of human MetAP2, and several amino acid side chains protruding into the binding pocket that differ between the plasmodial and human enzyme have been identified. The specific MetAP2 inhibitors, fumagilin and TNP-470, potently blocked in vitro growth of P. falciparum and Leishmania donovani, with IC50 values similar to the prototype drugs. Furthermore, in the case of P. falciparum, the chloroquine-resistant strains are equally susceptible to these two compounds.
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