The interfacial binding surface of phospholipase A2s
The interfacial binding surface of phospholipase A2s
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DOI：
10.1016/j.bbalip.2006.08.002
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发表时间：
2006-11-01
影响因子：
4.8
通讯作者：
Bahnson, Brian J.
中科院分区：
文献类型：
--
作者：
Winget, Jason M.;Pan, Ying H.;Bahnson, Brian J.
对于从聚集底物的单层或双层接触底物的膜相关酶来说，从水相到磷脂界面的分配对于催化至关重要。尽管关于界面酶的知识体系庞大且不断扩展，但对界面识别和吸附所涉及的生物物理步骤仍然知之甚少。酶与磷脂表面接触的表面称为其界面结合表面，或更简单地称为其 i 面。蛋白质的 i 面与聚集底物的相互作用可以简单地控制对底物的访问。然而，它可以更复杂，并且这种相互作用通常用于变构激活该表面上的酶。首先，我们简要回顾一下目前对典型界面酶（分泌型磷脂酶 A2 (PLA2)）的 i-face 结构和功能的了解。然后，我们开发、表征、比较和讨论五个同源 PLA2 家族成员（IA、IB、IIA、V 和 X 组）子集的 PLA2 i-face 模型。此比较中包括人类 V 组的同源模型，表明可以使用类似的方法来探索任何 PLA2 家族成员的界面功能。尽管序列同一性中等，但结构同源性和序列相似性仍然非常保守。我们发现预测为界面的残基虽然在结构上保守，但在序列上并不高度保守。讨论了这种分歧对界面选择性的影响。 (c) 2006 Elsevier B.V. 保留所有权利。
For membrane-associated enzymes, which access substrate from either a monolayer or bilayer of the aggregate substrate, the partitioning from the aqueous phase to this phospholipid interface is critical for catalysis. Despite a large and expanding body of knowledge regarding interfacial enzymes, the biophysical steps involved in interfacial recognition and adsorption remain relatively poorly understood. The surface of the enzyme that contacts the phospholipid surface is referred to as its interfacial binding surface, or more simply, its i-face. The interaction of a protein's i-face with the aggregate substrate may simply control access to substrate. However, it can be more complex, and this interaction often serves to allosterically activate the enzyme on this surface. First we briefly review what is currently known about i-face structure and function for a prototypical interfacial enzyme, the secreted Phospholipase A2 (PLA2). Then we develop, characterize, compare, and discuss models of the PLA2 i-face across a subset of five homologous PLA2 family members, groups IA, IB, IIA, V, and X. A homology model of human group-V is included in this comparison, suggesting that a similar approach could be used to explore interfacial function of any of the PLA2 family members. Despite moderate sequence identity, structural homology and sequence similarity are well conserved. We find that the residues predicted to be interfacial, while conserved structurally, are not highly conserved in sequence. Implications for this divergence on interfacial selectivity are discussed. (c) 2006 Elsevier B.V. All rights reserved.