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Cover Picture: Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3 (ChemBioChem 18/2008)
Author(s) -
AtillaGokcumen G. Ekin,
Pagano Nicholas,
Streu Craig,
Maksimoska Jasna,
Filippakopoulos Panagis,
Knapp Stefan,
Meggers Eric
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200890070
Subject(s) - ruthenium , gsk 3 , staurosporine , binding site , chemistry , natural product , stereochemistry , active site , enzyme , biochemistry , kinase , protein kinase a , catalysis
The cover picture shows the binding of a ruthenium half‐sandwich complex to the ATP binding site of glycogen synthase kinase 3 (GSK‐3) and how its structure and potency evolved from a brief structure–activity relationship. With a binding constant ( K i ) of, at most, 5 p M , this organometallic compound is several orders of magnitude more potent than the natural product staurosporine, which itself served as an inspiration for the design. The crystal structure of the organoruthenium inhibitor with GSK‐3 demonstrates that the metal itself is not involved in any direct interactions with the active site of GSK‐3, but solely serves as a structural center. Further details can be found in the article by E. Meggers, et al. on p. 2933 ff.