3qvn | pdb_00003qvn
Crystal Structure of cytosolic MnSOD3 from Candida albicans
Structural highlights
Function[Q96UT6_CANAX] Destroys radicals which are normally produced within the cells and which are toxic to biological systems (By similarity).[RuleBase:RU000414] Publication Abstract from PubMedHuman MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O(2)(-)). This behavior limits the amount of H(2)O(2) produced at high [O(2)(-)]; its desirability can be explained by the multiple roles of H(2)O(2) in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O(2)(-)], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn(3+) species in yeast Mn(3+)SODs, including the well-characterized 5-coordinate Mn(3+) species and a 6-coordinate L-Mn(3+) species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O(2)(-)]. Comparison of two yeast MnSODs: mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans.,Sheng Y, Stich TA, Barnese K, Gralla EB, Cascio D, Britt RD, Cabelli DE, Valentine JS J Am Chem Soc. 2011 Dec 28;133(51):20878-89. Epub 2011 Nov 30. PMID:22077216[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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