Document Detail

Agonists and partial agonists of rhodopsin: retinals with ring modifications.
MedLine Citation:
PMID:  16128569     Owner:  NLM     Status:  MEDLINE    
Activation of the visual pigment rhodopsin is initiated by isomerization of its retinal chromophore to the all-trans geometry, which drives the conformation of the protein to the active state. We have examined by FTIR spectroscopy the impact of a series of modifications at the ring of retinal on the activation process and on molecular interactions within the binding pocket. Deletion of ring methyl groups at C1 and C5 or replacement of the ring in diethyl or ethyl-methyl acyclic analogues resulted in partial agonists, for which the conformational equilibrium between the Meta I and Meta II photoproduct is shifted from the active Meta II side to the inactive Meta I side. While the Meta II states of these artificial pigments had a conformation similar to those of native Meta II, the Meta I states were different. Modifications on the ring of retinal had a particular impact on the interaction of Glu 122 within the ring-binding pocket and are shown to interfere with the Glu 134-mediated proton uptake during formation of Meta II. We further found, upon partial deletion of ring constituents, a decrease of the entropy change of the transition from Meta I to Meta II by up to 50%, while the concomitant reduction of the enthalpy term was less pronounced. These findings underline the particular importance of the ring and the ring methyl groups and are discussed in a model of receptor activation.
Reiner Vogel; Friedrich Siebert; Steffen Lüdeke; Amiram Hirshfeld; Mordechai Sheves
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  44     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-30     Completed Date:  2005-11-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11684-99     Citation Subset:  IM    
Biophysics Group, Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Strasse 9, D-79104 Freiburg, Germany.
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MeSH Terms
Models, Molecular
Protein Conformation
Retinaldehyde / analogs & derivatives*,  chemistry*
Rhodopsin / agonists*,  chemistry
Rod Opsins / chemistry
Signal Transduction
Spectroscopy, Fourier Transform Infrared
Structure-Activity Relationship
Reg. No./Substance:
0/Rod Opsins; 116-31-4/Retinaldehyde; 60383-01-9/metarhodopsins; 9009-81-8/Rhodopsin
Erratum In:
Biochemistry. 2005 Sep 27;44(38):12914

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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