A pH Switch Controls Zinc Binding in Tomato Copper-Zinc Superoxide Dismutase

Kevin W. Sea, Alexander B. Taylor, Susan T. Thomas, Amir Liba, Isabelle B. Bergman, Stephen P. Holloway, Xiaohang Cao, Edith B. Gralla, Joan S. Valentine, Peter J Hart, Ahmad Galaleldeen

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1597-1608
Number of pages12
Issue number20
StatePublished - May 25 2021

ASJC Scopus subject areas

  • Biochemistry


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