Cupillard L, Koumanov K, Mattéi M G, Lazdunski M, Lambeau G
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Sophia Antipolis, 660 route des Lucioles, 06560 Valbonne, France.
J Biol Chem. 1997 Jun 20;272(25):15745-52. doi: 10.1074/jbc.272.25.15745.
Secretory phospholipases A2 (sPLA2s) represent a rapidly expanding family of structurally related enzymes found in mammals as well as in insect and snake venoms. In this report, a cDNA coding for a novel sPLA2 has been isolated from human fetal lung, and its gene has been mapped to chromosome 16p13.1-p12. The mature sPLA2 protein has a molecular mass of 13.6 kDa, is acidic (pI 5.3), and made up of 123 amino acids. Key structural features of the sPLA2 include: (i) a long prepropeptide ending with an arginine doublet, (ii) 16 cysteines located at positions that are characteristic of both group I and group II sPLA2s, (iii) a C-terminal extension typical of group II sPLA2s, (iv) and the absence of elapid and pancreatic loops that are characteristic of group I sPLA2s. Based on these structural properties, this sPLA2 appears as a first member of a new group of sPLA2s, called group X. A 1.5-kilobase transcript coding for the human group X (hGX) sPLA2 was found in spleen, thymus, and peripheral blood leukocytes, while a less abundant 0.8-kilobase transcript was detected in the pancreas, lung, and colon. When the hGX sPLA2 cDNA was expressed in COS cells, sPLA2 activity preferentially accumulated in the culture medium, indicating that hGX sPLA2 is an actively secreted enzyme. It is maximally active at physiological pH and with 10 mM Ca2+. hGX sPLA2 prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.
分泌型磷脂酶A2（sPLA2s）是一个结构相关酶的快速扩展家族，在哺乳动物以及昆虫和蛇毒中都有发现。在本报告中，从人胎儿肺中分离出了编码一种新型sPLA2的cDNA，其基因已定位到染色体16p13.1 - p12。成熟的sPLA2蛋白分子量为13.6 kDa，呈酸性（pI 5.3），由123个氨基酸组成。sPLA2的关键结构特征包括：（i）以精氨酸双联体结尾的长前原肽；（ii）16个半胱氨酸位于I组和II组sPLA2特有的位置；（iii）II组sPLA2典型的C末端延伸；（iv）缺乏I组sPLA2特有的眼镜蛇科和胰腺环。基于这些结构特性，这种sPLA2似乎是sPLA2新组的第一个成员，称为X组。在脾脏、胸腺和外周血白细胞中发现了编码人X组（hGX）sPLA2的1.5千碱基转录本，而在胰腺、肺和结肠中检测到较少丰度的0.8千碱基转录本。当hGX sPLA2 cDNA在COS细胞中表达时，sPLA2活性优先积累在培养基中，表明hGX sPLA2是一种主动分泌的酶。它在生理pH值和10 mM Ca2+条件下活性最高。hGX sPLA2相比于磷脂酰丝氨酸脂质体，更喜欢磷脂酰乙醇胺和磷脂酰胆碱脂质体。
