Use of Prophet and MMS-X Computer Graphics in the Study of the Cardiac Steroid Receptor Site of Na,K-ATPase

Dwight S. Fullerton, Eitaroki Tatsuji, Tamboue Deffo, Douglas C. Rohrer, Khalil Ahmed, Arthur H.L. From

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Many often conflicting models have been proposed to describe the biological roles of digitalis structure and conformation. This chapter discusses the use of prophet and MMS-X computer graphics in the study of the cardiac steroid receptor site of Na, K-ATPase. X-ray crystallography provides precise atomic coordinates for subsequent analysis of the NIH Prophet and MMS-X computer systems. The conformational flexibility of the molecules is examined with potential energy calculations for rotations of the bonds to the C-17 side group and to the first sugar. The structures are superimposed and distances among corresponding atoms are calculated in the chapter to provide a direct measure of the geometric differences. It has been reported that the relative position of the C-17 side-group carbonyl oxygen had a nearly perfect correlation with rat brain Na, K-ATPase inhibition. The chapter also presents few of the analogs examined, including the toad poison bufalin and the progestin chlormadinone acetate. MMS-X is used to generate van der Waals enclosure maps to represent apparent volumes required for the compounds at the “ouabain-binding site.”

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalCurrent Topics in Membranes and Transport
Volume19
Issue numberC
DOIs
StatePublished - Jan 1 1983

Bibliographical note

Funding Information:
Supported by the National Heart, Lung (HL21457).

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