Structural and dynamics implications of an effector-induced backbone amide cis-trans isomerization in Cytocrhome P450cam

ELIANA K. ASCIUTTO; JEFFRY D. MADURA; SUSAN SONDEJ POCHAPSKY; BO OUYANG; THOMAS C. POCHAPSKY

JOURNAL OF MOLECULAR BIOLOGY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2009 vol. 388 p. 801 - 814

0022-2836

AbstractExperimental evidence has been provided for a functionally relevant cis–trans isomerization of the Ile88–Pro89 peptide bond in cytochrome P450cam (CYP101). The isomerization is proposed to be a key element of the structural reorganization leading to the catalytically competent form of CYP101 upon binding of the effector protein putidaredoxin (Pdx). A detailed comparison of the results of molecular dynamics simulations on the cis and trans conformations of substrate- and carbonmonoxy-bound ferrous CYP101 with sequence-specific Pdx-induced structural perturbations identified by nuclear magnetic resonance is presented, providing insight into the structural and dynamic consequences of the isomerization. The mechanical coupling between the Pdx binding site on the proximal face of CYP101 and the site of isomerization is described.