@article{4cfd6bbe02314e1a8c546ceba622ef47,
title = "A pH Switch Controls Zinc Binding in Tomato Copper-Zinc Superoxide Dismutase",
abstract = "Copper-zinc superoxide dismutase (SOD1) is a major antioxidant metalloenzyme that protects cells from oxidative damage by superoxide anions (O2-). Structural, biophysical, and other characteristics have in the past been compiled for mammalian SOD1s and for the highly homologous fungal and bovine SOD1s. Here, we characterize the biophysical properties of a plant SOD1 from tomato chloroplasts and present several of its crystal structures. The most unusual of these structures is a structure at low pH in which tSOD1 harbors zinc in the copper-binding site but contains no metal in the zinc-binding site. The side chain of D83, normally a zinc ligand, adopts an alternate rotameric conformation to form an unusual bidentate hydrogen bond with the side chain of D124, precluding metal binding in the zinc-binding site. This alternate conformation of D83 appears to be responsible for the previously observed pH-dependent loss of zinc from the zinc-binding site of SOD1. Titrations of cobalt into apo tSOD1 at a similar pH support the lack of an intact zinc-binding site. Further characterization of tSOD1 reveals that it is a weaker dimer relative to human SOD1 and that it can be activated in vivo through a copper chaperone for the SOD1-independent mechanism.",
author = "Sea, {Kevin W.} and Taylor, {Alexander B.} and Thomas, {Susan T.} and Amir Liba and Bergman, {Isabelle B.} and Holloway, {Stephen P.} and Xiaohang Cao and Gralla, {Edith B.} and Valentine, {Joan S.} and Hart, {P. John} and Ahmad Galaleldeen",
note = "Funding Information: The X-ray Crystallography Core Laboratory and the Center for Analytical Ultracentrifugation of Macromolecular Assemblies are part of the Institutional Research Cores at the University of Texas Health Science Center at San Antonio and supported by the Office of the Vice President for Research and the Mays Cancer Center Drug Discovery and Structural Biology Shared Resources (National Institutes of Health Grant P30 CA054174). The authors also acknowledge Aram M. Nerissian, Ph.D., for his contribution to this work and Dr. Borries Demeler for his help with interpreting the AUC experiments. Funding Information: This work was supported by National Institute of Neurological Disorders and Stroke Grants R01-NS39112 (P.J.H.) and P01-NS04913 (J.S.V., D.R. Borchelt, and P.J.H.). A.G. was supported in part by a St. Mary{\textquoteright}s University Faculty Research Grant and the Biaggini Grant. I.B.B. supported by the MARC U*STAR Program at St. Mary{\textquoteright}s University (Grant 5T34GM008073-31). Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",
year = "2021",
month = may,
day = "25",
doi = "10.1021/acs.biochem.1c00133",
language = "English (US)",
volume = "60",
pages = "1597--1608",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "20",
}