NMR Studies of Ligand Carboxylate Group Interactions with Arginine Residues in Complexes of Lactobacillus casei Dihydrofolate Reductase with Substrates and Substrate Analogues

Birdsall, B.; Polshakov, V.I.; Feeney, J.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Web of Science, Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.

Авторы: Birdsall B., Polshakov V.I., Feeney J.
Журнал: Biochemistry
Том: 39
Номер: 32
Год издания: 2000
Издательство: American Chemical Society
Местоположение издательства: United States
Первая страница: 9819
Последняя страница: 9825
DOI: 10.1021/bi000728s
Аннотация: In a series of complexes of Lactobacillus casei dihydrofolate reductase (DHFR) formed with substrates and substrate analogues, the 1H/15N NMR chemical shifts for the guanidino group of the conserved Arg 57 residue were found to be sensitive to the mode of binding of their Hη protons to the charged oxygen atoms in ligand carboxylate groups. In all cases, Arg 57 showed four nonequivalent Hη signals indicating hindered rotation about the Nε−Cζ and Cζ−Nη bonds. The Hη12 and Hη22 protons have large downfield shifts as expected for a symmetrical end-on interaction with the ligand carboxylate group. The chemical shifts are essentially the same in the complexes with folate and p-aminobenzoyl-l-glutamate (PABG) and similar to those found previously for the methotrexate complex reflecting the strong and similar hydrogen bonds formed with the carboxylate oxygens. Interestingly, the rates of rotation about the Nε−Cζ bond for the complexes containing the weakly binding PABG fragment are almost identical to those measured in the complex with methotrexate, which binds 107 times more tightly. In the methotrexate complex, this rotation depends on correlated rotations about the Nε−Cζ bond of Arg 57 and the Cα−C‘ bond of the ligand glutamate α-carboxylate group. Thus, even in a fragment such as PABG, which has a much faster off-rate, the carboxylate group binds to the enzyme in a similar way to that in a parent molecule such as folate and methotrexate with the rotation about the Nε−Cζ bond of Arg 57 being essentially the same in all the different complexes.
Добавил в систему: Польшаков Владимир Иванович

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NMR Studies of Ligand Carboxylate Group Interactions with Arginine Residues in Complexes of Lactobacillus casei Dihydrofolate Reductase with Substrates and Substrate Analoguesстатья

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