4E4E
Crystal Structure of the Y34F mutant of Saccharomyces cerevisiae Manganese Superoxide Dismutase
Summary for 4E4E
Entry DOI | 10.2210/pdb4e4e/pdb |
Descriptor | Superoxide dismutase [Mn], mitochondrial, MANGANESE (II) ION (3 entities in total) |
Functional Keywords | mn superoxide dismutase, oxidoreductase |
Biological source | Saccharomyces cerevisiae (Baker's yeast) |
Cellular location | Mitochondrion matrix: P00447 |
Total number of polymer chains | 4 |
Total formula weight | 94318.45 |
Authors | Sheng, Y.,Cascio, D.,Valentine, J.S. (deposition date: 2012-03-12, release date: 2012-08-22, Last modification date: 2023-09-13) |
Primary citation | Sheng, Y.,Butler Gralla, E.,Schumacher, M.,Cascio, D.,Cabelli, D.E.,Selverstone Valentine, J. Six-coordinate manganese(3+) in catalysis by yeast manganese superoxide dismutase. Proc.Natl.Acad.Sci.USA, 109:14314-14319, 2012 Cited by PubMed Abstract: Reduction of superoxide (O2-) by manganese-containing superoxide dismutase occurs through either a "prompt protonation" pathway, or an "inner-sphere" pathway, with the latter leading to formation of an observable Mn-peroxo complex. We recently reported that wild-type (WT) manganese superoxide dismutases (MnSODs) from Saccharomyces cerevisiae and Candida albicans are more gated toward the "prompt protonation" pathway than human and bacterial MnSODs and suggested that this could result from small structural changes in the second coordination sphere of manganese. We report here that substitution of a second-sphere residue, Tyr34, by phenylalanine (Y34F) causes the MnSOD from S. cerevisiae to react exclusively through the "inner-sphere" pathway. At neutral pH, we have a surprising observation that protonation of the Mn-peroxo complex in the mutant yeast enzyme occurs through a fast pathway, leading to a putative six-coordinate Mn(3+) species, which actively oxidizes O2- in the catalytic cycle. Upon increasing pH, the fast pathway is gradually replaced by a slow proton-transfer pathway, leading to the well-characterized five-coordinate Mn(3+). We here propose and compare two hypothetical mechanisms for the mutant yeast enzyme, differing in the structure of the Mn-peroxo complex yet both involving formation of the active six-coordinate Mn(3+) and proton transfer from a second-sphere water molecule, which has substituted for the -OH of Tyr34, to the Mn-peroxo complex. Because WT and the mutant yeast MnSOD both rest in the 2+ state and become six-coordinate when oxidized up from Mn(2+), six-coordinate Mn(3+) species could also actively function in the mechanism of WT yeast MnSODs. PubMed: 22908245DOI: 10.1073/pnas.1212367109 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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