Min K L, Steghens J P, Henry R, Doutheau A, Collombel C
Laboratoire de Biochimie C, Hôpital Edouard Herriot, Lyon, France.
Biochim Biophys Acta. 1997 Sep 26;1342(1):83-9. doi: 10.1016/s0167-4838(97)00088-5.
We describe a new compound, N-dibenzylphospho-N'-3-(2,6-dichlorophenyl)-propylguanidine (DPPG), and our study of its interaction with cytosolic CK. To our knowledge, it is the most potent inhibitor known for CK: the Ki value versus ADP was 330 nM and 110 nM for CK-MM and BB respectively. In view of the inhibition pattern, Ki(app) dependencies on the second substrate, and very low Ki values, we conclude that DPPG binds to the active site as a bisubstrate-type analog. This bisubstrate analog confirms different mechanisms for CK-MM and BB: in spite of a more than 80% similarity in amino-acid sequences, both isoenzymes are random at pH 8.6 but CK-BB has an ordered mechanism at pH 6.6.
