title: Comparison of two yeast MnSODs: mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans.
abstract: Human 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)(-)].
authors.affiliation: Department of Chemistry and Biochemistry, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, California 90095, USA.
authors.forename: Yuewei
authors.initials: Y
authors.lastname: Sheng
authors.forename: Troy A
authors.initials: TA
authors.lastname: Stich
authors.forename: Kevin
authors.initials: K
authors.lastname: Barnese
authors.forename: Edith B
authors.initials: EB
authors.lastname: Gralla
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.forename: R David
authors.initials: RD
authors.lastname: Britt
authors.forename: Diane E
authors.initials: DE
authors.lastname: Cabelli
authors.forename: Joan Selverstone
authors.initials: JS
authors.lastname: Valentine
mesh_terms: D002176:Candida albicans / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008958:Models, Molecular; D010084:Oxidation-Reduction; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase
references.citation: Biochim Biophys Acta. 2010 Feb;1804(2):245-62
references.pmid: 19914407
references.citation: Acc Chem Res. 2004 Jul;37(7):461-70
references.pmid: 15260508
references.citation: J Am Chem Soc. 2007 Aug 15;129(32):9927-40
references.pmid: 17628062
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: J Magn Reson. 2006 Jan;178(1):42-55
references.pmid: 16188474
references.citation: J Biol Chem. 1975 Aug 10;250(15):6107-12
references.pmid: 238997
references.citation: Biochemistry. 2009 Apr 21;48(15):3417-24
references.pmid: 19265433
references.citation: Biochemistry. 2005 Feb 8;44(5):1504-20
references.pmid: 15683235
references.citation: Nat Rev Mol Cell Biol. 2007 Sep;8(9):722-8
references.pmid: 17700625
references.citation: Mol Cell. 2007 Apr 13;26(1):1-14
references.pmid: 17434122
references.citation: Biochim Biophys Acta. 2010 Feb;1804(2):263-74
references.pmid: 19914406
references.citation: J Am Chem Soc. 2002 Sep 11;124(36):10833-45
references.pmid: 12207539
references.citation: Biochemistry. 1996 May 28;35(21):6762-70
references.pmid: 8639627
references.citation: Biochemistry. 2001 Apr 17;40(15):4622-32
references.pmid: 11294629
references.citation: J Am Chem Soc. 2001 Jun 20;123(24):5710-9
references.pmid: 11403603
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1295-305
references.pmid: 16910777
references.citation: Biochemistry. 2008 Feb 26;47(8):2350-6
references.pmid: 18247479
references.citation: J Mol Biol. 2010 Jun 11;399(3):377-84
references.pmid: 20417642
references.citation: J Am Chem Soc. 2010 Sep 15;132(36):12525-7
references.pmid: 20726524
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Chem Biol Interact. 2006 Mar 10;160(1):1-40
references.pmid: 16430879
references.citation: J Biol Chem. 2001 Dec 28;276(52):48662-9
references.pmid: 11598110
references.citation: Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):243-70
references.pmid: 16677071
references.citation: Biochemistry. 2000 Jun 20;39(24):7131-7
references.pmid: 10852710
references.citation: Biochemistry. 2001 Sep 4;40(35):10586-91
references.pmid: 11524001
references.citation: Free Radic Biol Med. 2000 Aug;29(3-4):222-30
references.pmid: 11035250
references.citation: J Immunol. 2002 Feb 1;168(3):1267-72
references.pmid: 11801664
references.citation: Biochemistry. 1997 Jul 22;36(29):8923-31
references.pmid: 9220980
references.citation: Structure. 2006 Nov;14(11):1617-22
references.pmid: 17098187
references.citation: Biochemistry. 2001 Oct 30;40(43):13079-87
references.pmid: 11669646
references.citation: Cell. 2005 Jun 3;121(5):667-70
references.pmid: 15935753
references.citation: J Mol Biol. 2000 Mar 3;296(4):951-9
references.pmid: 10686094
references.citation: Biochemistry. 2007 Dec 25;46(51):14830-7
references.pmid: 18044968
references.citation: Angew Chem Int Ed Engl. 2005 Jun 6;44(23):3613-6
references.pmid: 15864797
references.citation: Science. 2006 Jun 30;312(5782):1882-3
references.pmid: 16809515
references.citation: J Biol Chem. 2004 Mar 26;279(13):12769-76
references.pmid: 14688256
references.citation: Biochemistry. 1998 Apr 7;37(14):4731-9
references.pmid: 9537988
references.citation: Biochemistry. 2006 Feb 14;45(6):1919-29
references.pmid: 16460038
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Physiol Rev. 2002 Jan;82(1):47-95
references.pmid: 11773609
references.citation: Biochemistry. 1998 Apr 7;37(14):4722-30
references.pmid: 9537987
references.citation: Phys Chem Chem Phys. 2009 Aug 21;11(31):6614-25
references.pmid: 19639136
references.citation: J Am Chem Soc. 2002 Dec 18;124(50):15064-75
references.pmid: 12475351
references.citation: J Biol Chem. 2001 Nov 23;276(47):43784-91
references.pmid: 11562375
references.citation: Curr Opin Cell Biol. 2003 Apr;15(2):247-54
references.pmid: 12648682
references.citation: J Biol Chem. 2004 Aug 13;279(33):35079-86
references.pmid: 15180991
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Dec 1;64(Pt 12):1110-4
references.pmid: 19052361
references.citation: J Am Chem Soc. 2002 Apr 10;124(14):3482-3
references.pmid: 11929218
references.citation: Trends Biochem Sci. 2005 Apr;30(4):213-9
references.pmid: 15817398
references.citation: Biochemistry. 2001 Oct 9;40(40):12051-8
references.pmid: 11580280
references.citation: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references.pmid: 19461840
references.citation: Mol Aspects Med. 2004 Feb-Apr;25(1-2):17-26
references.pmid: 15051313
references.citation: Cell. 1992 Oct 2;71(1):107-18
references.pmid: 1394426
references.citation: Cell. 2008 Jul 25;134(2):279-90
references.pmid: 18662543
references.citation: Free Radic Res. 1997 Sep;27(3):283-9
references.pmid: 9350432
references.citation: J Am Chem Soc. 2005 Apr 27;127(16):6039-47
references.pmid: 15839704