ACTIVITY MODULATION OF PROTEIN KINASE AND PHOSPHATASE

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Phosphorylation/dephosphorylation is the most crucial chemical reaction taking place in living organisms, which is the basis for the regulatory control of many diverse biological events triggered by extracellular effectors. Our project involves the determination of the crystal structures of two protein kinases, AceK (also a protein phosphatase) and Etk, and a protein phosphatase, calcineurin. For AceK, which possesses both kinase and phosphatase activities, the kinase and phosphatase conformations of AceK, as well as AceK-ICDH complex structures will be solved for investigating the AceK activity switch and regulatory mechanism. The structures of full length membrane Etk, its mutants, and its complex with substrate Ugd will be determined. For calcineurin, which is a calmodulin-activated central controller of signaling in eukaryotes, we have created a fusion construct (known as CBA) to facilitate the structure determination of calmodulin-calcineurin complex, which would represent a structure of calmodulin in complex with an intact substrate.