Inactivation of the Na,K‐ATPase by modification of Lys‐501 with 4‐acetamido‐4′‐isothiocyanatostilbene‐2,2′‐disulfonic acid (SITS)

Abstract
The sodium pump or Na,K‐ATPase, maintains the Na+ and K+ gradients across eukaryotic cell membranes at the expense of ATP. Incubation of purified canine renal Na,K‐ATPase with 4‐acetamido‐4′‐isothiocyanatostilbene‐2,2′‐disulfonic acid (SITS) inhibited the ATPase activity. Both the labeling of the protein and the loss or ATPase activity were prevented by co‐incubation with ADP (acting as an ATP analog) or KCI. Only the α‐subunit was labeled by SITS. The α‐subunit from the inhibited enzyme was extensively digested with trypsin, and SITS‐labeled peptides were purified by reverse‐phase HPLC and sequenced. The amino acid sequence determined, His‐Leu‐Leu‐Val‐Met‐X‐Gly‐Ala‐Pro‐Glu, indicated that SITS modifies Lys‐501 (X) on the α‐subunit of Na,K‐ATPase.

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