Human prolidase and prolidase deficiency an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations
Human prolidase and prolidase deficiency an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations
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DOI：
10.1007/s00726-008-0055-4
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发表时间：
2008-11-01
期刊：
影响因子：
3.5
通讯作者：
Forlino, A.
中科院分区：
文献类型：
--
作者：
Lupi, A.;Tenni, R.;Forlino, A.
本文综述了目前已知的人氨酰基脯氨酸二肽酶的功能、结构和突变的影响。在肽酶中，氨酰基脯氨酸二肽酶是唯一切割在C-末端含有脯氨酸或羟脯氨酸残基的亚氨基二肽的金属酶。它与蛋白质代谢的最新阶段有关，特别是那些富含亚氨基酸的分子，如胶原蛋白，因此参与基质重塑。除了其细胞内功能外，氨酰基脯氨酸二肽酶对某些有机磷分子具有抗毒性作用，可用于饮食工业中作为苦味减轻剂，最近已被用作特异性黑色素瘤前药活化的靶酶。重组人脯氨酰二肽酶是在原核和真核宿主中产生的，具有与内源性酶相似的生化性质，并且代表了一种有效的工具，以更好地理解酶的结构和生物学功能，并开发用于脯氨酰二肽酶缺乏症（PD）的酶替代疗法。脯氨酰二肽酶缺乏症是一种罕见的隐性疾病，由脯氨酰二肽酶基因突变引起，其特征是严重的皮肤病变。单氨基酸取代、外显子剪接、缺失和重复被描述为引起该疾病的原因，并且主要位于来自不同物种的氨酰基脯氨酸二肽酶序列中的高度保守的氨基酸。PD的病理生理学仍然知之甚少，我们在这里提供了一个审查的分子机制，迄今为止假设。
Here we summarized what is known at the present about function, structure and effect of mutations in the human prolidase. Among the peptidases, prolidase is the only metalloenzyme that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end. It is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling. Beside its intracellular functions, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and recently has been used as target enzyme for specific melanoma prodrug activation. Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous enzyme and represents a valid tool both to better understand the structure and biological function of the enzyme and to develop an enzyme replacement therapy for the prolidase deficiency (PD). Prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions. Single amino acid substitutions, exon splicing, deletions and a duplication were described as causative for the disease and are mainly located at highly conserved amino acids in the sequence of prolidase from different species. The pathophysiology of PD is still poorly understood; we offer here a review of the molecular mechanisms so far hypothesized.