The conformational flexibility of 5,6,7,8‐tetrahydrobiopterin and 5,6,7,8‐tetrahydroneopterin: a molecular dynamical simulation

FEBS Letters

Estelberger, Willibald¹  Reibnegger, Gilbert¹  Mlekusch, Walter¹ 

[1] Medizinisch-Chemisches Institut und Pregl-Labor der Karl-Franzens-Universität Graz, Harrachgasse 21/II, A-8010 Graz, Austria

关键词: Pterin cofactor;    Molecular structure;    Molecular mechanics;    Molecular dynamics;   

DOI  :  10.1016/0014-5793(94)01302-H

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

5,6,7,8-Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6R,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 6R,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.

【 授权许可】

Unknown