title: The protein-folding speed limit: intrachain diffusion times set by electron-transfer rates in denatured Ru(NH3)5(His-33)-Zn-cytochrome c.
abstract: The kinetics of electron transfer from the triplet-excited Zn-porphyrin to a Ru(NH(3))(5)(His-33)(3+) complex have been measured in Zn-substituted ruthenium-modified cytochrome c under denaturing conditions. In the folded protein, the electron-tunneling rate constant is 7.5 x 10(5) s(-1). As the protein is denatured with guanidine hydrochloride, a faster adiabatic electron-transfer reaction appears (4.0 x 10(6) s(-1), [guanidine hydrochloride] = 5.4 M) that is limited by the rate of intrachain diffusion to bring the Zn-porphyrin and Ru complex into contact. The 250-ns contact time for formation of a 15-residue loop in denatured cytochrome c is in accord with a statistical model developed by Camacho and Thirumalai [Camacho, C. J. & Thirumalai, D. (1995) Proc. Natl. Acad. Sci. USA 92, 1277-1281] that predicts that the most probable transient loops formed in denatured proteins are comprised of 10 amino acids. Extrapolation of the cytochrome c contact time to a 10-residue loop sets the folding speed limit at approximately 10(7) s(-1).
authors.affiliation: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: I-Jy
authors.initials: IJ
authors.lastname: Chang
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lee
authors.forename: Jay R
authors.initials: JR
authors.lastname: Winkler
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
mesh_terms: D003574:Cytochrome c Group / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D045304:Cytochromes c; D004579:Electron Transport; D019791:Guanidine; D006639:Histidine; D007700:Kinetics; D046911:Macromolecular Substances; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012428:Ruthenium; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors; D015032:Zinc
chemical_list: D003574:Cytochrome c Group; D046911:Macromolecular Substances; D008665:Metalloporphyrins; D009942:Organometallic Compounds; C473938:Zn-cytochrome c, Ru(NH3)(5)His(33)-; C017802:zinc hematoporphyrin; D006639:Histidine; D013395:Sucrose; D012428:Ruthenium; D045304:Cytochromes c; D015032:Zinc; D019791:Guanidine