Identification of amino acids essential for estrone-3-sulfate transport within transmembrane domain 2 of organic anion transporting polypeptide 1B1.

PloS One
Nan LiMei Hong

Abstract

As an important structure in membrane proteins, transmembrane domains have been found to be crucial for properly targeting the protein to cell membrane as well as carrying out transport functions in transporters. Computer analysis of OATP sequences revealed transmembrane domain 2 (TM2) is among those transmembrane domains that have high amino acid identities within different family members. In the present study, we identify four amino acids (Asp70, Phe73, Glu74, and Gly76) that are essential for the transport function of OATP1B1, an OATP member that is specifically expressed in the human liver. A substitution of these four amino acids with alanine resulted in significantly reduced transport activity. Further mutagenesis showed the charged property of Asp70 and Glu74 is critical for proper function of the transporter protein. Comparison of the kinetic parameters indicated that Asp70 is likely to interact with the substrate while Glu74 may be involved in stabilizing the binding site through formation of a salt-bridge. The aromatic ring structure of Phe73 seems to play an important role because substitution of Phe73 with tyrosine, another amino acid with a similar structure, led to partially restored transport function. On the oth...Continue Reading

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Citations

Jul 28, 2016·Drug Metabolism and Pharmacokinetics·Xiaolin SunDi Zhao
Dec 13, 2016·Molecular Pharmaceutics·Chunxu NiMei Hong
Jun 1, 2017·Journal of Chemical Information and Modeling·Natalia KhuriKathleen M Giacomini
Nov 23, 2019·Endocrine Reviews·Stefan GroenewegW Edward Visser
Jun 10, 2021·Journal of Chemical Information and Modeling·Alzbeta TuerkovaBarbara Zdrazil

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Methods Mentioned

BETA
transfection
electrophoresis

Software Mentioned

ClustalW

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