220025-17-2Relevant academic research and scientific papers
Conformationally constrained analogues of diacylglycerol (DAG). 15.1 The indispensable role of the sn-1 and sn-2 carbonyls in the binding of dag- lactones to protein kinase C (PK-C)
Benzaria, Samira,Bienfait, Bruno,Nacro, Kassoum,Wang, Shaomeng,Lewin, Nancy E.,Beheshti, Maryam,Blumberg, Peter M.,Marquez, Victor E.
, p. 3403 - 3408 (1998)
The binding mode of DAG-lactones to PK-C was investigated using the C1b domain from the X-ray structure of the phorbol ester/C1b complex of PK-Cδ 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.
