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. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: Chembiochem. 2018 Dec 27;20(3):394–407. doi: 10.1002/cbic.201800593

Figure 3:

Figure 3:

Examples of silent (SAM), negative (NAM) and positive (PAM) allosteric modulators of the DGC enzyme DgcA. A) Structure and concentration response curve of the 1,3-benzoxazole-6-carboxylate derivative 1g, a silent allosteric regulator of DgcA. B) Representative example of an allosteric activator of the scaffold 1. The 4-nitrobenzoic acid derivative of 1h acts as a positive allosteric regulator with AC50 of 55.5 μM. The concentration response curves of the parental 1,3-benzothiazole-6-carboxylate 1 are shown as dashed lines in panels A and B. C) Structure and concentration response curve of 2a. Alteration of the methyl substituents from 2,5 to 2,4 in the 2 scaffold increases residual activity of the enzyme-substrate-inhibitor complex from 31.4% in 2 (dashed line) to 69.8% in 2a (closed circles). D) The 2-methoxy, 5-sulfonylmorpholine derivative 2b is a positive allosteric regulator with AC50 of 12.5 μM. Concentration response curves of the parental 2 are shown as dashed lines in panels C and D.