Conformationally constrained analogues of diacylglycerol (DAG).: 15.: The indispensable role of the sn-1 and sn-2 carbonyls in the binding of DAG-lactones to protein kinase C (PK-C)
Conformationally constrained analogues of diacylglycerol (DAG).: 15.: The indispensable role of the sn-1 and sn-2 carbonyls in the binding of DAG-lactones to protein kinase C (PK-C)
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DOI：
10.1016/s0960-894x(98)00614-3
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发表时间：
1998-12-01
影响因子：
2.7
通讯作者：
Marquez, VE
中科院分区：
文献类型：
--
作者：
Benzaria, S;Bienfait, B;Marquez, VE
以磷酸腺苷酯/磷酸腺苷-磷酸腺苷-磷酸腺苷-磷酸腺苷配合物的x射线结构C1b结构域为模板，研究了磷酸腺苷-内酯与磷酸腺苷-磷酸腺苷的结合模式。模型实验揭示了两种结合选择，其中DAG内酯的一个羰基与蛋白质不相关。然而，在实验中，去除sn-1或sn-2羰基会导致对PK-C的结合亲和力急剧下降。虽然不可能区分dag -内酯的两种结合选择，但研究表明附加羰基具有重要作用。这个基团的功能可能相当于酚酯中的C-9(OH)/C-13 （C=O）基序，在酚酯/C1b配合物中也没有相互作用。这一作用可能反映了在生物测定条件下与高亲和力结合所需的磷脂头基团的相互作用。1998爱思唯尔科学有限公司版权所有。
The binding mode of DAG-lactones to PK-C was investigated using the C1b domain from the Xray structure of the phorbol ester/C1b complex of PK-C delta as a template. Modeling experiments revealed two binding alternatives in which one of the carbonyls of the DAG lactones remained uninvolved with the protein. Experimentally, however, the removal of either sn-1 or sn-2 carbonyls caused a dramatic drop in binding affinity towards PK-C. Although it was not possible to discriminate between the two binding alternatives of the DAG-lactones, the study demonstrates an important role for the additional carbonyl group. The function of this group could be equivalent to that of the C-9(OH)/C-13 (C=O) motif in phorbol esters, which also appears free of interactions in the phorbol ester/C1b complex. This role presumably reflects interaction with the phosholipid head groups required for high affinity binding under the conditions of the biological assays. (C) 1998 Elsevier Science Ltd. All rights reserved.