Binding of bee venom and human group IIa phospholipases A2 to membranes: a minor role for electrostatics.
Binding of bee venom and human group IIa phospholipases A2 to membranes: a minor role for electrostatics.
复制标题
蜂毒和人类 IIa 族磷脂酶 A2 与膜的结合：静电的次要作用。
DOI：
10.1042/bst0260341
复制
发表时间：
1998
影响因子：
3.9
通讯作者：
Gelb,MH
中科院分区：
文献类型：
--
作者：
Lin,Y;Ghomashchi,F;Nielsen,R;Snitko,Y;Yu,BZ;Han,SK;Cho,W;Wilton,DC;Jain,MK;Robinson,BH;Gelb,MH
Phospholipases A2 (PLA2s) hydrolyse the sn-2 ester of phospholipids and have been studied extensively because of their role in liberating arachidonic acid from cellular membranes for the biosynthesis of eicosanoids [1, 2]. There are now 10 different PLA2 classes based on amino acid sequences [3, 4]. Many of these are small (-14-18 kDa), secreted, calcium-dependent enzymes found in snake, insect, and lizard venoms, animal digestive fluids, and inflammatory exudates (sPLA2s). The pancreatic, cobra venom, and bee venom sPLA2s have been extensively studied from a structure-function point of view and as a paradigm for the action of watersoluble enzymes at the lipid-water interface (interfacial enzymology)[5-91. T he availability of X-ray structures of several sPLA2s [lo] and the NMR structure of pancreatic sPLA2s [11,121 have provided the necessary components for studying the molecular basis for interfacial binding and catalysis [13-161. In some cases, structure-function studies have been interpreted in terms of an analytical kinetic reaction scheme for interfacial catalysis [8, 9]. sPLA2s bind tightly to anionic vesiclesAlthough it is certain that sPLA2s must transfer from the aqueous phase to the membrane interface to hydrolyse naturally occurring long-chain phospholipids that have virtually no solubility in water (ie lipolysis by phospholipase A2 necessarily occurs at the interface [17]), until recently there was limited information on the molecular determinants of interfacial binding of these enzymes. The X-ray structures of sPLA2s reveal a deep (-15A) active site slot that accommodates about half of the length of a phospholipid molecule. The catalytic residues lie at the end of
