Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family
Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family
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DOI：
10.1016/j.biochi.2006.09.021
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发表时间：
2007-02-01
期刊：
影响因子：
3.9
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Aoki, Junken;Inoue, Asuka;Arai, Hiroyuki
磷脂酶A（1）（PLA（1））是一种水解磷脂并产生2-酰基溶血磷脂和脂肪酸的酶，并且在广泛的生物体中是保守的。哺乳动物有几种酶在体外表现出PLA（1）活性。胞外PLA（1）包括磷脂酰丝氨酸（PS）特异性PLA（1）（PS-PLA（1））、膜结合磷脂酸（PA）选择性PLA（1）（mPA-PLA（1）α和mPA-PLA（1）β）、肝脂肪酶（HL）、内皮脂肪酶（EL）和胰脂肪酶相关蛋白2（PLRP 2），它们都属于胰脂肪酶基因家族。前三个PLA（1）在底物特异性、结构特征和基因组织方面与其他成员不同，构成胰脂肪酶基因家族的一个亚家族。PS-PLA（1）、mPA-PLA（1）α和mPA-PLA（1）β仅表现出PLA（1）活性，而HL、EL和PLRP 2除了PLA（1）活性之外还表现出三酰甘油水解活性。脂肪酶的三级结构具有两个表面环，盖和β 9环。盖和β 9环覆盖其闭合构象的活性位点。胰脂肪酶基因家族成员的氨基酸序列的比对揭示了两个表面环中PLAIs的两个分子特征。首先，表现出PLA（1）活性的脂肪酶成员（PS-PLA（1）、mPA-PLA（1）α和mPA-PLA（1）β、EL、豚鼠PLRP 2和PLA，来自大黄蜂毒液（Dolml））具有短盖。其次，仅表现出PLA 1活性的PS-PLA（1）、mPA-PLA（1）α、mPA-PLA（1）β和Dolml具有短β 9环。因此，这两个表面环似乎参与配体识别。PS-PLA（1）和mPA-PLA（1）分别特异性水解PS和PA，产生它们相应的溶血磷脂。溶血磷脂酰丝氨酸和溶血磷脂酸是具有多种生物学功能的脂质介质。因此，这些PLAI在这些溶血磷脂介质的产生中起作用。(c)2006年，Elsevier Masson SAS。All rights reserved.
Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Mammals have several enzymes that exhibit PLA(1) activity in vitro. The extracellular PLA(1)s include phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)), membrane-associatedphosphatidic acid (PA)-selectivePLA(1)s (mPA-PLA(1)alpha and mPA-PLA(1)beta), hepatic lipase (HL), endothelial lipase (EL) and pancreatic lipase-related protein 2 (PLRP2), all of which belong to the pancreatic lipase gene family. The former three PLA(1)s differ from other members in their substrate specificities, structural features and gene organizations, and form a subfamily in the pancreatic lipase gene family. PS-PLA(1), mPA-PLA(1)alpha and mPA-PLA(1)beta exhibit only PLA(1) activity, while HL, EL and PLRP2 show triacylglycerol-hydrolyzing activity in addition to PLA(1) activity. The tertiary structures of lipases have two surface loops, the lid and the beta 9 loop. The lid and the beta 9 loop cover the active site in its closed conformation. An alignment of amino acid sequences of the pancreatic lipase gene family members revealed two molecular characteristics of PLAIs in the two surface loops. First, lipase members exhibiting PLA(1) activity (PS-PLA(1), mPA-PLA(1)alpha and mPA-PLA(1)beta, EL, guinea pig PLRP2 and PLA, from hornet venom (Dolml)) have short lids. Second, PS-PLA(1), mPA-PLA(1)alpha, mPA-PLA(1)beta and Dolml, which exhibit only PLA, activity, have short beta 9 loops. Thus, the two surface loops appear to be involved in the ligand recognition. PS-PLA(1) and mPA-PLA(1)s specifically hydrolyze PS and PA, respectively, producing their corresponding lysophospholipids. Lysophosphatidylserine and lysophosphatidic acid have been defined as lipid mediators with multiple biological functions. Thus, these PLAIs have a role in the production of these lysophospholipid mediators. (c) 2006 Elsevier Masson SAS. All rights reserved.