2jdo: Difference between revisions

Although the crystal structure of the anti-cancer target protein kinase B, (PKBbeta/Akt-2) has been useful in guiding inhibitor design, the closely, related kinase PKA has generally been used as a structural mimic due to, its facile crystallization with a range of ligands. The use of, PKB-inhibitor crystallography would bring important benefits, including a, more rigorous understanding of factors dictating PKA/PKB selectivity, and, the opportunity to validate the utility of PKA-based surrogates. We, present a "back-soaking" method for obtaining PKBbeta-ligand crystal, structures, and provide a structural comparison of inhibitor binding to, PKB, PKA, and PKA-PKB chimera. One inhibitor presented here exhibits no, PKB/PKA selectivity, and the compound adopts a similar binding mode in all, three systems. By contrast, the PKB-selective inhibitor A-443654 adopts a, conformation in PKB and PKA-PKB that differs from that with PKA. We, provide a structural explanation for this difference, and highlight the, ability of PKA-PKB to mimic the true PKB binding mode in this case.

2JDO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with I5S and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JDO OCA].  

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