title: Cysteine-based redox switches in enzymes.
abstract: The enzymes involved in metabolism and signaling are regulated by posttranslational modifications that influence their catalytic activity, rates of turnover, and targeting to subcellular locations. Most prominent among these has been phosphorylation/dephosphorylation, but now a distinct class of modification coming to the fore is a set of versatile redox modifications of key cysteine residues. Here we review the chemical, structural, and regulatory aspects of such redox regulation of enzymes and discuss examples of how these regulatory modifications often work in concert with phosphorylation/dephosphorylation events, making redox dependence an integral part of many cell signaling processes. Included are the emerging roles played by peroxiredoxins, a family of cysteine-based peroxidases that now appear to be major players in both antioxidant defense and cell signaling.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Chananat
authors.initials: C
authors.lastname: Klomsiri
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Karplus
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Poole
mesh_terms: D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D004798:Enzymes; D054464:Peroxiredoxins; D003545:Cysteine
references.citation: Nature. 2005 May 19;435(7040):347-53
references.pmid: 15902258
references.citation: Biochemistry. 2002 Jan 29;41(4):1293-301
references.pmid: 11802729
references.citation: Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):243-70
references.pmid: 16677071
references.citation: Methods Enzymol. 2010;473:77-94
references.pmid: 20513472
references.citation: Curr Opin Chem Biol. 1998 Oct;2(5):633-41
references.pmid: 9818190
references.citation: Cell. 2004 May 28;117(5):625-35
references.pmid: 15163410
references.citation: Antioxid Redox Signal. 2009 May;11(5):997-1014
references.pmid: 18999917
references.citation: J Biol Chem. 2006 Apr 14;281(15):10420-30
references.pmid: 16418165
references.citation: Science. 2007 Sep 7;317(5843):1393-7
references.pmid: 17717153
references.citation: Arch Biochem Biophys. 2002 Jan 15;397(2):312-8
references.pmid: 11795888
references.citation: J Alzheimers Dis. 2010;20(2):369-93
references.pmid: 20164570
references.citation: J Cell Biol. 2008 Jun 30;181(7):1129-39
references.pmid: 18573911
references.citation: J Biol Chem. 2004 Jun 18;279(25):26159-66
references.pmid: 15075328
references.citation: J Biol Chem. 2007 Jul 27;282(30):22011-22
references.pmid: 17519234
references.citation: J Biol Chem. 2002 Jun 7;277(23):20336-42
references.pmid: 11916965
references.citation: Mol Cell Biol. 2005 Aug;25(15):6391-403
references.pmid: 16024778
references.citation: Science. 2003 Apr 25;300(5619):650-3
references.pmid: 12714747
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9633-8
references.pmid: 18606987
references.citation: Biochemistry. 2006 Jul 18;45(28):8476-87
references.pmid: 16834321
references.citation: Circ Res. 2007 Feb 2;100(2):213-9
references.pmid: 17185628
references.citation: Chem Res Toxicol. 2008 Sep;21(9):1832-40
references.pmid: 18698849
references.citation: J Biol Chem. 1998 Dec 4;273(49):32554-60
references.pmid: 9829991
references.citation: Antioxid Redox Signal. 2009 Jun;11(6):1289-99
references.pmid: 18999986
references.citation: ACS Chem Biol. 2010 Apr 16;5(4):405-14
references.pmid: 20146502
references.citation: Cell. 2010 Feb 19;140(4):454-6
references.pmid: 20178737
references.citation: ACS Chem Biol. 2010 Jan 15;5(1):47-62
references.pmid: 19957967
references.citation: Free Radic Biol Med. 2000 May 1;28(9):1349-61
references.pmid: 10924854
references.citation: Methods Enzymol. 2010;473:95-115
references.pmid: 20513473
references.citation: J Biol Chem. 2007 Apr 20;282(16):11885-92
references.pmid: 17329258
references.citation: Free Radic Biol Med. 2006 May 1;40(9):1539-48
references.pmid: 16632114
references.citation: Free Radic Biol Med. 2009 Oct 15;47(8):1162-71
references.pmid: 19646526
references.citation: FEBS Lett. 2002 Apr 24;517(1-3):229-32
references.pmid: 12062443
references.citation: J Biol Chem. 2002 Oct 11;277(41):38029-36
references.pmid: 12161445
references.citation: FEBS J. 2008 Jan;275(1):69-88
references.pmid: 18067579
references.citation: Biochemistry. 1994 May 17;33(19):5974-83
references.pmid: 8180227
references.citation: Annu Rev Biochem. 1985;54:305-29
references.pmid: 2862840
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19839-44
references.pmid: 19064914
references.citation: Mol Cell. 2008 Jan 18;29(1):36-45
references.pmid: 18206967
references.citation: J Biol Chem. 2002 May 31;277(22):19396-401
references.pmid: 11904290
references.citation: Science. 2002 Aug 16;297(5584):1186-90
references.pmid: 12183632
references.citation: J Biol Chem. 2001 Sep 7;276(36):33393-401
references.pmid: 11445563
references.citation: Mol Cell Proteomics. 2010 Jul;9(7):1400-10
references.pmid: 20233844
references.citation: Trends Biochem Sci. 2003 Jan;28(1):32-40
references.pmid: 12517450
references.citation: Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1819-27
references.pmid: 16987034
references.citation: Curr Opin Chem Biol. 2008 Feb;12(1):18-24
references.pmid: 18282483
references.citation: Biochemistry. 2010 Feb 9;49(5):835-42
references.pmid: 20050630
references.citation: Free Radic Res. 2006 Dec;40(12):1250-8
references.pmid: 17090414
references.citation: Biochem J. 2004 Aug 1;381(Pt 3):675-83
references.pmid: 15139849
references.citation: FEBS J. 2009 May;276(9):2469-77
references.pmid: 19476488
references.citation: Biochem Pharmacol. 1999 Jul 1;58(1):133-43
references.pmid: 10403526
references.citation: Cell. 2005 Jun 3;121(5):667-70
references.pmid: 15935753
references.citation: Free Radic Biol Med. 2008 Aug 15;45(4):494-502
references.pmid: 18501718
references.citation: J Biol Chem. 2010 Mar 5;285(10):7505-16
references.pmid: 20061379
references.citation: Biochemistry. 1999 Oct 12;38(41):13574-83
references.pmid: 10521264
references.citation: Cell. 2010 Feb 19;140(4):517-28
references.pmid: 20178744
references.citation: Biochemistry. 1998 Apr 21;37(16):5633-42
references.pmid: 9548949
references.citation: Science. 2006 Jun 30;312(5782):1882-3
references.pmid: 16809515
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18742-7
references.pmid: 18003920
references.citation: J Biol Chem. 2003 Dec 12;278(50):50226-33
references.pmid: 14522978
references.citation: J Immunol. 2007 Nov 15;179(10):6456-67
references.pmid: 17982034
references.citation: J Mol Biol. 2010 Jan 29;395(4):844-59
references.pmid: 19854201
references.citation: FEBS Lett. 2005 Mar 21;579(8):1891-5
references.pmid: 15763569
references.citation: J Biol Chem. 2003 Aug 29;278(35):33408-15
references.pmid: 12816947
references.citation: Biochem Pharmacol. 2008 Jun 1;75(11):2234-44
references.pmid: 18395187
references.citation: Biochemistry. 2004 Jun 15;43(23):7356-64
references.pmid: 15182179
references.citation: Biochemistry. 2003 Sep 2;42(34):10060-70
references.pmid: 12939134
references.citation: Chem Res Toxicol. 2001 Oct;14(10):1453-64
references.pmid: 11599938
references.citation: Biochemistry. 2007 Jan 23;46(3):709-19
references.pmid: 17223692
references.citation: J Biol Chem. 2005 Jan 28;280(4):2750-8
references.pmid: 15533936
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):813-24
references.pmid: 17848967
references.citation: Biochemistry. 2000 Sep 12;39(36):11121-8
references.pmid: 10998251
references.citation: FEBS Lett. 1999 Jun 11;452(3):219-22
references.pmid: 10386594
references.citation: Biochemistry. 2008 Dec 2;47(48):12860-8
references.pmid: 18986167
references.citation: J Bacteriol. 2001 Dec;183(24):7173-81
references.pmid: 11717276
references.citation: Curr Opin Pharmacol. 2007 Aug;7(4):381-91
references.pmid: 17662654
references.citation: J Cell Biol. 2006 Dec 4;175(5):779-89
references.pmid: 17145963
references.citation: Cell Cycle. 2009 Aug;8(15):2353-5
references.pmid: 19571676
references.citation: J Biol Chem. 2008 Apr 11;283(15):9986-98
references.pmid: 18250162
references.citation: J Biol Chem. 2001 Nov 2;276(44):41279-87
references.pmid: 11533038
references.citation: Antioxid Redox Signal. 2005 May-Jun;7(5-6):560-77
references.pmid: 15890001
references.citation: Protein Sci. 2008 Feb;17(2):299-312
references.pmid: 18227433
references.citation: Protein Sci. 2008 Mar;17(3):473-81
references.pmid: 18287280
references.citation: EMBO J. 1998 Oct 1;17(19):5543-50
references.pmid: 9755155
references.citation: Science. 1998 May 8;280(5365):895-8
references.pmid: 9572732
references.citation: Biochemistry. 2005 Aug 9;44(31):10583-92
references.pmid: 16060667
references.citation: Free Radic Biol Med. 2008 Sep 1;45(5):549-61
references.pmid: 18544350
references.citation: Trends Biochem Sci. 2009 Feb;34(2):85-96
references.pmid: 19135374
references.citation: Biochemistry. 2009 Feb 17;48(6):1399-409
references.pmid: 19166311
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8197-202
references.pmid: 18287020
references.citation: Annu Rev Biochem. 2008;77:755-76
references.pmid: 18173371
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:325-47
references.pmid: 14744249
references.citation: J Biol Chem. 2005 Aug 5;280(31):28775-84
references.pmid: 15941719