Slowing of Proton Transport Processes in the Structure of Bacterial Reaction Centers and Bacteriorhodopsin in the Presence of Dipyridamole

P. P. Knox^1*, E. P. Lukashev¹, M. D. Mamedov², A. Yu. Semenov², N. H. Seifullina¹, and N. I. Zakharova¹

¹Department of Biophysics, School of Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (7-095) 939-1115; E-mail: knox@biophys.msu.ru

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (7-095) 939-3188; E-mail: semenov@electro.genebee.msu.su

^* To whom correspondence should be addressed.

Received April 26, 1999; Revision received May 14, 1999

---

Dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido(5,4-d)pyrimidine, is employed in clinical practice as a vasodilator. It can also inhibit a specific membrane protein (glycoprotein P) which pumps anticancer drugs out of tumor cells. Dipyridamole (10^-4 M) markedly slows down the kinetics of the electrogenic phase of the photoelectric response in Rhodobacter sphaeroides chromatophores. This phase is due to proton transfer from the external medium to the secondary quinone acceptor in the reaction center. In purple membranes of bacterium Halobacterium salinarium containing bacteriorhodopsin dipyridamole (in its charged state) significantly slowed the kinetics of proton transfer from the primary donor, Asp-96 (in membranes from bacteria of wild type), or from the external medium (in D96N mutant) to the Schiff base. It is suggested that dipyridamole can influence the structural-dynamic state of membrane proteins including modification of the structure of their hydrogen bonds involved in proton-transport processes.

---

KEY WORDS: reaction center of bacteria, bacteriorhodopsin, proton transport, dipyridamole, Rhodobacter sphaeroides, Halobacterium salinarium

---