- 作者: Peng Zhang, Diarmuid E. Nicholson, Janusz M. Buinicki, Xinzhuan Su, James J. Brendle, Michael Ferdig, Dennis E. Kyle, Wilbur K. MIlhous, Peter K. Chiang
- 作者服務機構: Walter Reed Army Institute of Research, Silver Spring, Md., Walter Reed Army Medical Center, Washington, D.C. , National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA; International Institute of Molecular and Cell Biology, Warsaw, Poland
- 中文摘要: --
- 英文摘要: Leishmania donavani, with IC values similar to the pro-totype drugs. Furthermore, in the case of P. falciparum,the chloroquine-resistant strains are equally susceptibleto these two compounds.Methionine aminopeptidase 2 (MetAP2) is responsiblefor the hydrolysis of the initiator methionine moleculefrom the majority of newly synthesized proteins. Wehave cloned the MetAP2 gene from the malaria parasitePlasmodium falciparum (PfMetAP2; GenBank accessionnumber AF348320). The cloned PfMetAP2 has no intron,consists of 1,544 bp and encodes a protein of 354 aminoacids with a molecular mass of 40,537D and an overallbase composition of 72.54% A+T. PfMetAP2 has 40%sequence identity with human MetAP2 and 45% identitywith yeast MetAP2, and is located in chromosome 14 ofP. falciparum. The three-dimensional structure of PfMetAP2 has been modeled based on the crystal structureof human MetAP2, and several amino acid side chainsprotruding into the binding pocket that differ betweenthe plasmodial and human enzyme have been identified.The specific MetAP2 inhibitors, fumagillin and TNP-470,potently blocked in vitro growth of P. falciparum and
- 中文關鍵字: --
- 英文關鍵字: Angiogenesis, Malaria, Leishmaniasis, Methionine, Aminopeptidase, Fumagillin, TNP-470