X-Ray Structure of Balanol (PDB-code 1BX6)
The complex of the natural (-)-balanol with PKA (PDB-code 1BX6) was solved in 1999 (Narayana et al. 1999). The molecule (Fig. 7) can be considered in terms of occupation of three regions of the ATP binding pocket: a phenol (Fig. 7, ring A) in the adenine subsite, an azepane (B) in the ribose subsite and the benzophenone (C and D) occupies the triphosphate subsite.
The phenol makes two H-bonds from the -OH group to the hinge region Val123(N) and Glu121(0); VDW contacts exist to Leu49, Ala70, Glu121, Tyr122, Val123, Thr183 and Phe327. The amide that links to the azepane ring makes one H-bond to a water molecule with its amide nitrogen and to Thr183 with its carbonyl oxygen. The azepane ring is in VDW contact with Gly50, Glu127 and Glu170, and additionally forms an H-bond with Gly170. The benzophenone part interacts with Thr51, Gly52, Ser53, Phe54, Gly55, Arg56, Lys72, Leu74, Gln84, Glu91, Asp184, Gly186, Phe187. Benzophenone substituents are involved in several H-bonds: to Gly52, Ser53, Phe54, and
Gly55 from the glycine loop, to the conserved residues Lys72 and Glu91, and to Asp184 from the beginning of the activation loop.
In total, there are 21 H-bonds and 114 VDW interactions, whereas most occur with the triphosphate subsite (Narayana et al. 1999; Setyawan et al. 1999; Wong et al. 2001).
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