Protein kinases structural biology

Also related to Src kinase structural biology have been studies on two SFKs, namely Lck and Fyn. Importantly, the X-ray structure of Lck kinase was the first SFK determined [64] as complexes with AMP-PNP, staurosporine and PP2. Furthermore, a Fyn kinase-staurosporine complex has been recently described [65]. Extrapolating from the above Src kinase inhibitor crystal structures with respect to the hydrophobic specificity pocket and the active conformation of the protein to bind ATP-competitive inhibitors of varying templates and functional group elaboration, a working hypothesis of known Src kinase inhibitors (vide infra) can be suggested (Fig. 4). 

A worldwide repository for the processing and distribution of three-dimensional biologic macromolecular structure data.) The Protein Kinase Resource http //pkr.sdsc.edu/html/index. shtml... 

AKT-1 kinase (also called protein kinase B or PKBa) is a serine/threonine kinase belonging to the AGC kinase family [1], AKT was identified from a viral oncogene, v-akt, found in tumor lines established from spontaneous thymomas found in AKR mice [2]. Subsequently, two more AKT isoforms, AKT-2 (or PKB(3) and AKT-3 (or PKBy) have been identified [3]. Reviews exist detailing the structural and cell biology of AKT and the reader is referred to these for further information [4,7,12]. 

Takahashi 1, Saitoh Y, Yoshida M, Sano H, Nakano H, Morimoto M, Tamaoki T. (1989) UCN-01 and UCN-02, new selective inhibitors of protein kinase C. 11. Purification, physico-chemical properties, structural determination and biological activities. J Antibiot 42 571-576. 

Newton, A.C. (1995) Protein kinase C structure, function, and regulation. Journal of Biological Chemistry 270, 28495-28498. 

CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Bruce E. Maryanoff and Cynthia A. Maryanoff. Computer Assisted Molecular Design Related to the Protein Kinase C Receptor, Paul A. Wenderand Cynthia M. Cribbs. Chemistry and Biology of the Immunosuppressant (-)-FK-506, Ichiro Shinkai and Nolan H. Sigal. The Development of Ketorolac Impact on Pyrrole Chemistry and on Pain Therapy, Joseph M. Muchowski. Application of Silicon Chemistry in the Corticosteroid Field, Douglas A. Livingston. Hu-perzine A-A Possible Lead Structure in the Treatment of Alzheimers Disease, Alan P. Kozikowski, X.C, Tang and Israel Hanin. Mechanism-Based-Dual-Action Cephalosporins, Harry A. Albrecht and James G. Christenson. Some Thoughts on Enzyme Inhibitors and the Quiescent Affinity Label Concept, Mien Krantz Index. 

Scapin, G. Structural biology in drug design selective protein kinase inhibitors. Drug Discov. Today 2002, 7, 601-611. 

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