Magro Angelo J, Soares Andreimar M, Giglio José R, Fontes Marcos R M
Departamento de Física e Biofísica, IB, UNESP, Botucatu-SP, Brazil.
Biochem Biophys Res Commun. 2003 Nov 21;311(3):713-20. doi: 10.1016/j.bbrc.2003.10.047.
Phospholipases A(2) are components of Bothrops venoms responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. A class of PLA(2)-like proteins has been described which despite PLA(2) activity on artificial substrate, due to a D49K mutation, is still highly myonecrotic. This work reports the X-ray structure determination of two Lys49-PLA(2)s from Bothrops neuwiedi pauloensis (BnSP-7 and BnSP-6) and, for the first time, the comparison of eight dimeric Lys49-PLA(2)s. This comparison reveals that there are not just two ("open" and "closed") but at least six different conformations. The binding of fatty acid observed in three recent Lys49-PLA(2) structures seems to be independent of their quaternary conformation. Cys29 polarization by Lys122 is not significant for BnSP-7 and BnSP-6 or other structures not bound by fatty acids. These structures may be in an "active" state when nothing is bound to them and the Lys122/Cys29 interactions are weak or absent.
磷脂酶A(2)是具窍蝰蛇毒液的成分，可通过水解细胞膜磷脂来破坏细胞膜完整性。已描述了一类PLA(2)样蛋白，尽管其对人工底物具有PLA(2)活性，但由于D49K突变，其仍具有高度的肌坏死性。这项工作报道了两种来自保罗具窍蝰蛇（BnSP - 7和BnSP - 6）的Lys49 - PLA(2)的X射线结构测定，并且首次对8种二聚体Lys49 - PLA(2)进行了比较。该比较表明，不仅存在两种（“开放”和“闭合”）构象，而且至少有六种不同的构象。在最近的三种Lys49 - PLA(2)结构中观察到的脂肪酸结合似乎与其四级构象无关。对于BnSP - 7和BnSP - 6或其他未被脂肪酸结合的结构，Lys122对Cys29的极化作用并不显著。当没有任何物质与之结合且Lys122/Cys29相互作用较弱或不存在时，这些结构可能处于“活性”状态。
