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Ligand Binding Sites of Na, K-ATPase.

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Title: Ligand Binding Sites of Na, K-ATPase.
Authors: Lingrel, J. B., Croyle, M. L., Woo, A. L., Argüello, J. M.
Source: Acta Physiologica Scandinavica. Aug98 Supplement 643, Vol. 163, p69. 9p. 3 Diagrams, 1 Graph.
Subjects: Ligand binding (Biochemistry), Sodium/potassium ATPase
Abstract: Our studies have concentrated on two aspects of the Na,K-ATPase, the first relates to the identification of amino acids involved in binding Na[sup+] and K[sup+] during the catalytic cycle and the second involves defining how cardiac glycosides inhibit the enzyme. To date, three amino acids, Ser775, Asp804 and Asp808, all located in transmembrane regions five and six, have been shown to play a major role in K[sup+] binding. These findings are based on site directed mutagenesis and expression studies. In order to understand how cardiac glycosides interact with the Na,K-ATPase, studies again involving mutagenesis coupled with expression have been used. More specifically, amino acid residues have been substituted in an ouabain sensitive α subunit using random mutagenesis, and the ability of the resulting enzyme to confer resistance to ouabain sensitive cells was determined. Interestingly, the amino acids of the α subunit which alter ouabain sensitivity cluster in two major regions, one comprised of the first and second transmembrane spanning domains and the extracellular loop joining them, and the second formed by the extracellular halves of transmembrane regions four, five, six and seven. As noted above, transmembrane regions five and six also contain the three amino acid residues Ser775, Asp804 and Asp808 which play a key role in cation transport, possibly binding K[sup+]. Thus, it is reasonable to propose that cardiac glycosides bind to two sites, the N- terminal region and the central region which contains the cation binding sites. Cardiac glycoside binding to the center region may lock the cation transport region into a configuration such that the enzyme cannot go through the conformational change required for ion transport. [ABSTRACT FROM AUTHOR]
Copyright of Acta Physiologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Group: Ti
  Data: Ligand Binding Sites of Na, K-ATPase.
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  Data: <searchLink fieldCode="AR" term="%22Lingrel%2C+J%2E+B%2E%22">Lingrel, J. B.</searchLink><br /><searchLink fieldCode="AR" term="%22Croyle%2C+M%2E+L%2E%22">Croyle, M. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Woo%2C+A%2E+L%2E%22">Woo, A. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Argüello%2C+J%2E+M%2E%22">Argüello, J. M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Acta+Physiologica+Scandinavica%22">Acta Physiologica Scandinavica</searchLink>. Aug98 Supplement 643, Vol. 163, p69. 9p. 3 Diagrams, 1 Graph.
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  Data: <searchLink fieldCode="DE" term="%22Ligand+binding+%28Biochemistry%29%22">Ligand binding (Biochemistry)</searchLink><br /><searchLink fieldCode="DE" term="%22Sodium%2Fpotassium+ATPase%22">Sodium/potassium ATPase</searchLink>
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  Label: Abstract
  Group: Ab
  Data: Our studies have concentrated on two aspects of the Na,K-ATPase, the first relates to the identification of amino acids involved in binding Na[sup+] and K[sup+] during the catalytic cycle and the second involves defining how cardiac glycosides inhibit the enzyme. To date, three amino acids, Ser775, Asp804 and Asp808, all located in transmembrane regions five and six, have been shown to play a major role in K[sup+] binding. These findings are based on site directed mutagenesis and expression studies. In order to understand how cardiac glycosides interact with the Na,K-ATPase, studies again involving mutagenesis coupled with expression have been used. More specifically, amino acid residues have been substituted in an ouabain sensitive α subunit using random mutagenesis, and the ability of the resulting enzyme to confer resistance to ouabain sensitive cells was determined. Interestingly, the amino acids of the α subunit which alter ouabain sensitivity cluster in two major regions, one comprised of the first and second transmembrane spanning domains and the extracellular loop joining them, and the second formed by the extracellular halves of transmembrane regions four, five, six and seven. As noted above, transmembrane regions five and six also contain the three amino acid residues Ser775, Asp804 and Asp808 which play a key role in cation transport, possibly binding K[sup+]. Thus, it is reasonable to propose that cardiac glycosides bind to two sites, the N- terminal region and the central region which contains the cation binding sites. Cardiac glycoside binding to the center region may lock the cation transport region into a configuration such that the enzyme cannot go through the conformational change required for ion transport. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Acta Physiologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Code: eng
        Text: English
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        PageCount: 9
        StartPage: 69
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      – SubjectFull: Ligand binding (Biochemistry)
        Type: general
      – SubjectFull: Sodium/potassium ATPase
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      – TitleFull: Ligand Binding Sites of Na, K-ATPase.
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            NameFull: Woo, A. L.
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            – D: 02
              M: 08
              Text: Aug98 Supplement 643
              Type: published
              Y: 1998
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