曼氏血吸虫成虫腺嘌呤核苷磷酸化酶的分离及底物特异性
Isolation and substrate specificity of an adenine nucleoside phosphorylase from adult Schistosoma mansoni.
作者信息
Savarese Todd M, El Kouni Mahmoud H
机构信息
Division of Biology and Medicine, Brown University, RI 02912, USA.
Division of Biology and Medicine, Brown University, RI 02912, USA; Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
出版信息
Mol Biochem Parasitol. 2014 Mar-Apr;194(1-2):44-7. doi: 10.1016/j.molbiopara.2014.04.008. Epub 2014 Apr 30.
An adenine nucleoside phosphorylase (ANP, EC none) activity was identified and partially purified from extracts of Schistosoma mansoni by chromatofocussing column chromatography and molecular sieving. The enzyme is distinct from purine nucleoside phosphorylase (PNP, EC 2.4.2.1). ANP is specific for adenine nucleosides which includes adenosine analogs modified in the aglycone, pentose or both moieties. (e.g. 2'-deoxyadenosine, 5'-deoxy-5'-methylthioadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, etc.) The enzyme is also distinct from the mammalian 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP, EC 2.4.2.28) in that it is able of the phosphorolysis of 2'-deoxyadenosine while mammalian MTAP cannot. Because of ANP unique substrate specificity, the enzyme could play a role as a target for chemotherapy of these parasites. Cytotoxic analogs may be designed as subversive substrates that are selectively activated only by the schistosomal ANP.
通过聚焦层析柱色谱法和分子筛法，从曼氏血吸虫提取物中鉴定并部分纯化了一种腺嘌呤核苷磷酸化酶（ANP，酶委员会编号未给出）活性。该酶与嘌呤核苷磷酸化酶（PNP，酶委员会编号2.4.2.1）不同。ANP对腺嘌呤核苷具有特异性，这些核苷包括在糖苷配基、戊糖或两个部分都经过修饰的腺苷类似物（例如2'-脱氧腺苷、5'-脱氧-5'-甲硫基腺苷、5'-脱氧-5'-碘-2-氟腺苷等）。该酶也与哺乳动物的5'-脱氧-5'-甲硫基腺苷磷酸化酶（MTAP，酶委员会编号2.4.2.28）不同，因为它能够磷酸解2'-脱氧腺苷，而哺乳动物的MTAP则不能。由于ANP独特的底物特异性，该酶可能作为这些寄生虫化疗的靶点发挥作用。细胞毒性类似物可设计为仅被血吸虫ANP选择性激活的颠覆性底物。
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