Cléry-Barraud Cécile, Renault Frédérique, Leva Julien, El Bakdouri Nacéra, Masson Patrick, Rochu Daniel
Centre de Recherches du Service de Santé des Armées, Département de Toxicologie, BP 87, 38702 La Tronche cedex, France.
Biochim Biophys Acta. 2009 Apr;1794(4):680-8. doi: 10.1016/j.bbapap.2009.01.003. Epub 2009 Jan 29.
Human paraoxonase-1 (HuPON1) is the ideal candidate to engineer as catalytic bioscavenger for pre-treatment and therapy of exposure to toxic organophosphorus compounds. HuPON1 is a naturally-occurring hydrophobic plasma protein associated with a partner, the human phosphate binding protein (HPBP) on high density lipoproteins. The relationships between the composition and the size of multimeric states of HuPON1 are not well understood. Moreover, the effect of HPBP's presence on enzyme catalysis and stability is not clear. The effect of hydrostatic pressure on structural stability and activity of different PON1 preparations (free natural HuPON1 or in the presence of 50% w/w HPBP, hybrid recombinant PON1) was investigated. Results showed that PON1 exists under several multimeric forms, and that the binding of HPBP amends the size of the hetero-oligomeric states and exerts a stabilizing effect on the activities of PON1. Furthermore, high pressure kinetic experiments highlighted the fact that PON1 displays two distinct catalytic behaviors: the first one for arylesterase and lactonase activities and the second one for its organophosphate-hydrolase activity.
人对氧磷酶-1（HuPON1）是作为催化性生物清除剂用于有毒有机磷化合物暴露的预处理和治疗的理想候选物。HuPON1是一种天然存在的疏水性血浆蛋白，与高密度脂蛋白上的伴侣——人磷酸盐结合蛋白（HPBP）相关。HuPON1多聚体状态的组成与大小之间的关系尚未完全了解。此外，HPBP的存在对酶催化和稳定性的影响尚不清楚。研究了静水压力对不同PON1制剂（游离天然HuPON1或存在50% w/w HPBP、杂交重组PON1）的结构稳定性和活性的影响。结果表明，PON1以几种多聚体形式存在，并且HPBP的结合改变了杂合寡聚体状态的大小，并对PON1的活性产生稳定作用。此外，高压动力学实验突出了PON1表现出两种不同催化行为这一事实：第一种是芳基酯酶和内酯酶活性，第二种是其有机磷酸酯水解酶活性。
