Methods in enzymology

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers protein kinase inhibitors in research and medicine, and includes chapters on such topics as fragment-based screening, broad kinome profiling of kinase inhibitors, and designing drug-resistant kinase alleles. Continues the legacy of this premier serial with quality chapters authored by leaders in the field Covers research methods in biomineralization scienceContains sections focusing on protein kinase inhibitors in research and medicine.

Front Cover; Protein Kinase Inhibitors in Research and Medicine ; Copyright; Contents; Contributors; Preface; Chapter One: Catalytic Mechanisms and Regulation of Protein Kinases; 1. Introduction; 2. Kinetic Mechanism; 3. Chemical Mechanism of Kinase Phosphoryl Transfer; 4. Applications of Mechanistic Studies in Understanding Kinase Function and Regulation; 4.1. Bisubstrate analogs; 4.2. Oncogenic kinase mutants; 4.3. Chemical rescue of tyrosine kinases; 5. Summary and Outlook; References; Chapter Two: A Structural Atlas of Kinases Inhibited by Clinically Approved Drugs; 1. Introduction.

2. Kinase Structure and Catalytic Mechanism3. Staurosporine: A Promiscuous ATP-Competitive Inhibitor; 4. BCR-Abl Inhibitors; 4.1. Imatinib binds to a ``DFG-out ́ ́ Abl conformation; 4.2. Nilotinib (Tasigna): An imatinib analog effective against several imatinib-resistant Abl variants; 4.3. Ponatinib (Iclusig) overcomes an Abl gatekeeper resistance mutation; 4.4. Bosutinib (Bosulif) inhibits BCR-Abl; 4.5. Dasatinib (Sprycel) binds to a ``DFG-in ́ ́ conformation of Abl; 5. Tofacitinib (Xeljanz) Binds to a ``DFG-in ́ ́ Conformation of Janus Kinase; 6. Inhibition of Receptor Tyrosine Kinases.

6.1. Imatinib…