A proposed role for Leishmania major carboxypeptidase in peptide catabolism.
A proposed role for Leishmania major carboxypeptidase in peptide catabolism.
复制标题
利什曼原虫主要羧肽酶在肽分解代谢中的拟议作用。
DOI：
10.1016/j.bbrc.2008.05.162
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发表时间：
2008
影响因子：
3.1
通讯作者：
Chan,MichaelK
中科院分区：
文献类型：
--
作者：
Isaza,ClaraE;Zhong,Xuejun;Rosas,LuciaE;White,JamesD;Chen,RitaP-Y;Liang,GeorgeF-C;Chan,SunneyI;Satoskar,AbhayR;Chan,MichaelK
利什曼病是一种由利什曼原虫引起的热带疾病，利什曼原虫是一种通过白蛉传播给人类的真核寄生虫。为了开发这种疾病的新化疗靶点，对硕大利什曼原虫（LmaCP 1）基因组中存在的两种M32羧肽酶之一进行了生物化学和体内表达研究。酶学研究表明，像以前研究的M32羧肽酶，LmaCP 1裂解底物的各种C-末端氨基酸的主要例外是那些具有C-末端酸性残基。用一系列基于FRET的肽进行的切割测定表明，LmaCP 1表现出底物长度限制，优选短于9-12个氨基酸的肽。分析了LmaCP 1在L.主要生命周期这些研究表明，LmaCP 1的表达只发生在前环前鞭毛体的生命阶段，其中生物体居住在腹部中肠的昆虫。这些结果的影响进行了讨论。
Leishmaniasis is a tropical disease caused by Leishmania, eukaryotic parasites transmitted to humans by sand flies. Towards the development of new chemotherapeutic targets for this disease, biochemical and in vivo expression studies were performed on one of two M32 carboxypeptidases present within the Leishmania major (LmaCP1) genome. Enzymatic studies reveal that like previously studied M32 carboxypeptidases, LmaCP1 cleaves substrates with a variety of C-terminal amino acids—the primary exception being those having C-terminal acidic residues. Cleavage assays with a series of FRET-based peptides suggest that LmaCP1 exhibits a substrate length restriction, preferring peptides shorter than 9–12 amino acids. The in vivo expression of LmaCP1 was analyzed for each major stage of the L. major life cycle. These studies reveal that LmaCP1 expression occurs only in procyclic promastigotes—the stage of life where the organism resides in the abdominal midgut of the insect. The implications of these results are discussed.