Fasudil is related to H7, and has a heptameric homopiperazine ring at the position of the methyl-piperazine ring of H7 (Table 1).
The binding of fasudil is similar to the binding of the parental molecule H7 to PKA (Engh et al. 1996) (Fig. 3). The essential hydrogen bond between the peptide backbone amide of Val123 and the nitrogen atom of the iso-quinoline ring is formed. As H7, the secondary amine of the homopiper-azine ring makes a hydrogen contact to the peptide backbone carbonyl of Glu170. This contact, usually reserved for the 3' OH of ATP, is present in the PKA/H7 structure too. Not provided by H7, fasudil can make, in addition, a contact of the homopiperazine nitrogen to the sidechain of Glu127. In the
ATP structure this contact is also present, to the 2' and 3' OH groups of the ribose.
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