Structural highlights
Disease
[SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
Function
[SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human manganese superoxide dismutase (MnSOD) is characterized by a product inhibition stronger than that observed in bacterial forms of MnSOD. Previous studies show that the conserved, active-site residue Tyr34 mediates product inhibition; however, the protein environment of Tyr34 is different in human and Escherichia coli MnSOD. We have prepared two site-specific mutants of human MnSOD with replacements of Phe66 with Ala and Leu (F66A and F66L, respectively), altering the surroundings of Tyr34. Pulse radiolysis was used to generate superoxide, and measurements of catalysis were taken in single-turnover experiments by observing the visible absorbance of species of MnSOD and under catalytic conditions observing the absorbance of superoxide. The mutation of Phe66 to Leu resulted in a mutant of human MnSOD with weakened product inhibition resembling that of E. coli MnSOD. Moreover, the mechanism of this weakened product inhibition was similar to that in E. coli MnSOD, specifically a decrease in the rate constant for the oxidative addition of superoxide to Mn2+MnSOD leading to the formation of the peroxide-inhibited enzyme. In addition, the crystal structures of both mutants have been determined and compared to those of wild-type human and E. coli MnSOD. The crystallographic data suggest that the solvent structure and its mobility as well as side chain conformations may affect the extent of product inhibition. These data emphasize the role of residue 66 in catalysis and inhibition and provide a structural explanation for differences in catalytic properties between human and certain bacterial forms of MnSOD.
Structural and kinetic study of differences between human and Escherichia coli manganese superoxide dismutases.,Zheng J, Domsic JF, Cabelli D, McKenna R, Silverman DN Biochemistry. 2007 Dec 25;46(51):14830-7. Epub 2007 Nov 29. PMID:18044968[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999 Jun 1;366(1):82-8. PMID:10334867 doi:S0003-9861(99)91202-X
- ↑ Zheng J, Domsic JF, Cabelli D, McKenna R, Silverman DN. Structural and kinetic study of differences between human and Escherichia coli manganese superoxide dismutases. Biochemistry. 2007 Dec 25;46(51):14830-7. Epub 2007 Nov 29. PMID:18044968 doi:10.1021/bi7014103
