Eight Amino Acids Form the ATP Recognition Site of Na+/K+-ATPase

Abstract
Point mutations of a part of the H4−H5 loop (Leu354−Ile604) of Na+/K+-ATPase have been used to study the ATP and TNP-ATP binding affinities. Besides the previously reported amino acid residues Lys480, Lys501, Gly502, and Cys549, we have found four more amino acid residues, viz., Glu446, Phe475, Gln482, and Phe548, completing the ATP-binding pocket of Na+/K+-ATPase. Moreover, mutation of Arg423 has also resulted in a large decrease in the extent of ATP binding. This residue, localized outside the binding pocket, seems to play a key role in supporting the proper structure and shape of the binding site, probably due to formation of a hydrogen bond with Glu472. On the other hand, only some minor effects were caused by mutations of Ile417, Asn422, Ser445, and Glu505.

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