Document Type
Article
Publication Date
2-2006
Source Publication
Biochemistry
Abstract
Conformational flexibility of the enzyme architecture is essential for biological function. These structural transitions often encompass significant portions of the enzyme molecule. Here, we present a detailed study of functionally relevant RNase A dynamics in the wild type and a D121A mutant form by NMR spin-relaxation techniques. In the wild-type enzyme, the dynamic properties are largely conserved in the apo, enzyme−substrate, and enzyme−product complexes. In comparison, mutation of aspartic acid 121 to alanine disrupts the timing of active-site dynamics, the product-release step, and global conformational changes, indicating that D121 plays a significant role in coordinating the dynamic events in RNase A. In addition, this mutation results in 90% loss of catalytic activity despite the absence of direct participation of D121 in the chemical reaction or in interactions with the substrate. These data suggest that one role of this conserved residue is to facilitate important millisecond protein dynamics.
Recommended Citation
Kovriguine, Evgueni and Loria, J. Patrick, "Enzyme Dynamics Along the Reaction Coordinate: Critical Role of a Conserved Residue" (2006). Chemistry Faculty Research and Publications. 233.
https://epublications.marquette.edu/chem_fac/233
Comments
Accepted version. Biochemistry, Vol. 45, No. 8 (February 2006): 2636-2647. DOI. © 2006 American Chemical Society (ACS). Used with permission.