Experimental and Theoretical Analysis of the Steric Tolerance of the Binding Site of Bacterioopsin with the Use of Side-Chain Methyl-Shifted Retinal Analogs

Angel R. de Lera, Beatriz Iglesias, Rosana Alvarez, Susana López, Jesús Rodríguez, Xavier Villanueva, Esteve Padrós

Research output: Contribution to journalArticleResearchpeer-review

55 Citations (Scopus)

Abstract

Four positional isomers of trans-retinal (1) differing in the location of the side-chain methyl groups have been prepared by a combination of Wittig and highly stereocontrolled Suzuki coupling reactions. The incubation of 9-demethyl-10-methylretinal (5) with bacterioopsin yielded an artificial pigment with an opsin shift of 4630 cm–1. The other three analogs, namely 13-demethyl-14-methylretinal (3), 13-demethyl-12-methylretinal (4), and 9-demethyl-8-methylretinal (6) did not bind to the apoprotein. In order to rationally address the intrinsic structural differences among analogs which could be relevant to the discrimination exhibited by the protein binding site, ab initio calculations with complete optimization at the 3-21G level were performed on model N-methylretinal iminium salts derived from aldehydes 1 and 3–6. The validity of the approach was inferred from the remarkable coincidence between the minimized structure of N-methylretinal Schiff base (PSB-1) and the structural parameters displayed by N-methyl-N-phenylretinal iminium perchlorate (38b). Computations clearly show that the location of the methyl groups on the polyene side chain is of the utmost importance in determining the overall shape of the retinal ligands. Those structural effects, added to the dominant steric and electronic restrictions of the binding pocket, would explain the observed discrimination among the analogs 3–6, with minor structural changes, and perhaps among other retinals reported in the literature. Additionally, the theoretical and experimental results obtained with 9-demethyl-8-methylretinal (6) provide further indirect evidence of the importance of the 6-s-trans conformation for the native chromophore in bacteriorhodopsin. © 1995, American Chemical Society. All rights reserved.
Original languageEnglish
Pages (from-to)8220-8231
JournalJournal of the American Chemical Society
Volume117
Issue number31
DOIs
Publication statusPublished - 1 Jan 1995

Fingerprint Dive into the research topics of 'Experimental and Theoretical Analysis of the Steric Tolerance of the Binding Site of Bacterioopsin with the Use of Side-Chain Methyl-Shifted Retinal Analogs'. Together they form a unique fingerprint.

  • Cite this