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Establishing the entatic state in folding metallated Pseudomonas aeruginosa azurin

Zong, Chenghang and Wilson, Corey J. and Shen, Tongye and Wittung-Stafshede, Pernilla and Mayo, Stephen L. and Wolynes, Peter G. (2007) Establishing the entatic state in folding metallated Pseudomonas aeruginosa azurin. Proceedings of the National Academy of Sciences of the United States of America, 104 (9). pp. 3159-3164. ISSN 0027-8424. PMCID PMC1805512. https://resolver.caltech.edu/CaltechAUTHORS:ZONpnas07

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805512/PubMed CentralArticle
ORCID:
AuthorORCID
Wittung-Stafshede, Pernilla0000-0003-1058-1964
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.
Funders:
Funding AgencyGrant Number
NSF0610425
Gordon and Betty Moore FoundationP449351
NIHGM44557
NIHGM059663
Robert A. Welch FoundationC-1588
Subject Keywords:curved chevron, cupredoxin, metalloproteins
Issue or Number:9
PubMed Central ID:PMC1805512
Record Number:CaltechAUTHORS:ZONpnas07
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:ZONpnas07
Alternative URL:http://dx.doi.org/10.1073/pnas.0611149104
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8632
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:01 Sep 2007
Last Modified:02 Oct 2019 23:52

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