Structural Differences in Triosephosphate Isomerase from Different Species and Discovery of a Multitrypanosomatid Inhibitor

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• 作者：Vanesa Olivares-Illana ; Ruy P&eacute ; rez-Montfort ; Francisco Ló ; pez-Calahorra ; Miguel Costas ; Adela Rodrí ; guez-Romero ; Marieta Tuena de Gó ; mez-Puyou ; and Armando Gó ; mez Puyou
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：February 28, 2006
• 年：2006
• 卷：45
• 期：8
• 页码：2556 - 2560
• 全文大小：106K
• 年卷期：v.45,no.8(February 28, 2006)
• ISSN：1520-4995

文摘

We examined the interfaces of homodimeric triosephosphate isomerase (TIM) from eightdifferent species. The crystal structures of the enzymes showed that a portion of the interface is markedlysimilar in TIMs from Trypanosoma cruzi (TcTIM), Trypanosoma brucei, and Leishmania mexicana andsignificantly different from that of TIMs from human, yeast, chicken, Plasmodium falciparum, andEntamoeba histolytica. Since this interfacial region is central in the stability of TcTIM, we hypothesizedthat it would be possible to find agents that selectively affect the stability of TIMs from the threetrypanosomatids. We found that 6,6'-bisbenzothiazole-2,2' diamine in the low micromolar range causesa desirable irreversible inactivation of the enzymes from the three trypanosomatids and has no effect onthe other five TIMs. Thus, the data indicate that it is possible to find compounds that induce selectiveinactivation of the enzymes from three different trypanosomatids.