Chemical modification as an approach to elucidation of sodium pump structure-function relations.
Chemical modification of specific residues in enzymes, with the characterization of the type of inhibition and properties of the modified activity, is an established approach in structure-function studies of proteins. This strategy has become more productive in recent years with the advances made in obtaining primary sequence information from gene-cloning technologies. This article discusses the application of chemical modification procedures to the study of the Na(+)-K(+)-ATPase protein. A wide array of information has become available about the kinetics, enzyme structure, and various conformational states as a result of the combined use of inhibitors, ligands, modifiers, and proteolytic enzymes. We will review a variety of reagents and approaches that have been employed to arrive at structure-function correlates and discuss critically the limits and ambiguities in the type of information obtained from these methodologies. Chemical modification of the Na(+)-pump protein has already provided a body of data and will, we anticipate, guide the efforts of mutagenesis studies in the future when suitable expression systems become available.
Pedemonte
C H
CH
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
Kaplan
J H
JH
D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology; D008954:Models, Biological; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013329:Structure-Activity Relationship
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase