Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published February 27, 2007 | Supplemental Material + Published
Journal Article Open

Establishing the entatic state in folding metallated Pseudomonas aeruginosa azurin


Understanding how the folding of proteins establishes their functional characteristics at the molecular level challenges both theorists and experimentalists. The simplest test beds for confronting this issue are provided by electron transfer proteins. The environment provided by the folded protein to the cofactor tunes the metal's electron transport capabilities as envisioned in the entatic hypothesis. To see how the entatic state is achieved one must study how the folding landscape affects and in turn is affected by the metal. Here, we develop a coarse-grained functional to explicitly model how the coordination of the metal (which results in a so-called entatic or rack-induced state) modifies the folding of the metallated Pseudomonas aeruginosa azurin. Our free-energy functional-based approach directly yields the proper nonlinear extra-thermodynamic free energy relationships for the kinetics of folding the wild type and several point-mutated variants of the metallated protein. The results agree quite well with corresponding laboratory experiments. Moreover, our modified free-energy functional provides a sufficient level of detail to explicitly model how the geometric entatic state of the metal modifies the dynamic folding nucleus of azurin.

Additional Information

© 2007 by the National Academy of Sciences. Contributed by Peter G. Wolynes, December 15, 2006 (received for review December 11, 2006). Published online before print February 14, 2007, 10.1073/pnas.0611149104 We thank Jay R. Winkler and Harry B. Gray for helpful suggestions throughout the project and critical comments on the manuscript. Support for this project was provided by National Science Foundation Grant 0610425 (to C.J.W.), Gordon E. Moore Foundation Grant P449351 (to C.J.W.), National Institutes of Health Grants GM44557 (to P.G.W.) and GM059663 (to P.W.-S.), and Robert A. Welch Foundation Grant C-1588 (to P.W.-S.). Author contributions: C.Z., C.J.W., T.S., P.W.-S., S.L.M., and P.G.W. designed research; C.Z., C.J.W., and T.S. performed research; C.Z. and C.J.W. analyzed data; and C.Z., C.J.W., and P.G.W. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0611149104/DC1.

Attached Files

Published - ZONpnas07.pdf

Supplemental Material - ZONpnas07supfig6.pdf

Supplemental Material - ZONpnas07supfig7.pdf

Supplemental Material - ZONpnas07supfig8.pdf


Files (2.0 MB)
Name Size Download all
573.0 kB Preview Download
25.3 kB Preview Download
1.1 MB Preview Download
308.5 kB Preview Download

Additional details

August 22, 2023
October 16, 2023