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The conformational flexibility of 5,6,7,8‐tetrahydrobiopterin and 5,6,7,8‐tetrahydroneopterin: a molecular dynamical simulation
Author(s) -
Estelberger Willibald,
Mlekusch Walter,
Reibnegger Gilbert
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01302-h
Subject(s) - tetrahydrobiopterin , chemistry , cofactor , molecular dynamics , flexibility (engineering) , molecular mechanics , stereochemistry , computational chemistry , molecule , quantum chemical , conformational ensembles , enzyme , biochemistry , organic chemistry , mathematics , statistics
5,6,7,8‐Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6 R ,1′ R ,2′ S ‐configuration is biologically active. Other stereoisomers, as well as other reduced pterins such as, e.g. 5,6,7,8‐tetrahydroneopterin, fail to exhibit significant cofactor activity. Different theoretical models (molecular mechanics, semi‐empirical quantum chemical calculations) investigating the stereostructure of tetrahydrobiopterin have yielded diverging answers. It has been claimed on the basis of semi‐empirical quantum chemical calculations that conformational properties, and thus particular features in overall shape, might be responsible for the unique biological properties of natural tetrahydrobiopterin in contrast, e.g. to 6 R ,1′ S ,2′ R ‐5,6,7,8‐tetrahydroneopterin. Molecular dynamical simulations of both molecules at realistic temperatures demonstrate, however, that they possess sufficient conformational flexibility as to render questionable any biological significance of mere conformational properties.