Source:http://linkedlifedata.com/resource/pubmed/id/15475355
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
53
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| pubmed:dateCreated |
2004-12-23
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| pubmed:abstractText |
Little is known about the molecular mechanism of Schiff base hydrolysis in rhodopsin. We report here our investigation into this process focusing on the role of amino acids involved in a hydrogen bond network around the retinal Schiff base. We find conservative mutations in this network (T94I, E113Q, S186A, E181Q, Y192F, and Y268F) increase the activation energy (E(a)) and abolish the concave Arrhenius plot normally seen for Schiff base hydrolysis in dark state rhodopsin. Interestingly, two mutants (T94I and E113Q) show dramatically faster rates of Schiff base hydrolysis in dark state rhodopsin, yet slower hydrolysis rates in the active MII form. We find deuterium affects the hydrolysis process in wild-type rhodopsin, exhibiting a specific isotope effect of approximately 2.5, and proton inventory studies indicate that multiple proton transfer events occur during the process of Schiff base hydrolysis for both dark state and MII forms. Taken together, our study demonstrates the importance of the retinal hydrogen bond network both in maintaining Schiff base integrity in dark state rhodopsin, as well as in catalyzing the hydrolysis and release of retinal from the MII form. Finally, we note that the dramatic alteration of Schiff base stability caused by mutation T94I may play a causative role in congenital night blindness as has been suggested by the Oprian and Garriga laboratories.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
31
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| pubmed:volume |
279
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
55886-94
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15475355-Amino Acid Sequence,
pubmed-meshheading:15475355-Animals,
pubmed-meshheading:15475355-COS Cells,
pubmed-meshheading:15475355-Cattle,
pubmed-meshheading:15475355-Deuterium Oxide,
pubmed-meshheading:15475355-Genetic Vectors,
pubmed-meshheading:15475355-Hot Temperature,
pubmed-meshheading:15475355-Hydrogen Bonding,
pubmed-meshheading:15475355-Hydrolysis,
pubmed-meshheading:15475355-Hydroxylamine,
pubmed-meshheading:15475355-Kinetics,
pubmed-meshheading:15475355-Models, Chemical,
pubmed-meshheading:15475355-Models, Molecular,
pubmed-meshheading:15475355-Molecular Sequence Data,
pubmed-meshheading:15475355-Mutagenesis, Site-Directed,
pubmed-meshheading:15475355-Mutation,
pubmed-meshheading:15475355-Protein Conformation,
pubmed-meshheading:15475355-Protein Structure, Tertiary,
pubmed-meshheading:15475355-Protons,
pubmed-meshheading:15475355-Retina,
pubmed-meshheading:15475355-Rhodopsin,
pubmed-meshheading:15475355-Spectrometry, Fluorescence,
pubmed-meshheading:15475355-Spectrophotometry,
pubmed-meshheading:15475355-Thermodynamics,
pubmed-meshheading:15475355-Time Factors,
pubmed-meshheading:15475355-Ultraviolet Rays
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| pubmed:year |
2004
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| pubmed:articleTitle |
Role of the retinal hydrogen bond network in rhodopsin Schiff base stability and hydrolysis.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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