Fast ferrous heme-NO oxidation in nitric oxide synthases.
During catalysis, the heme in nitric oxide synthase (NOS) binds NO before releasing it to the environment. Oxidation of the NOS ferrous heme-NO complex by O2 is key for catalytic cycling, but the mechanism is unclear. We utilized stopped-flow methods to study the reaction of O2 with ferrous heme-NO complexes of inducible and neuronal NOS enzymes. We found that the reaction does not involve heme-NO dissociation, but instead proceeds by a rapid direct reaction of O2 with the ferrous heme-NO complex. This behavior is novel and may distinguish heme-thiolate enzymes, such as NOS, from related heme proteins.
Tejero
Jesús
J
Department of Pathobiology, The Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Santolini
Jérôme
J
Stuehr
Dennis J
DJ
D000818:Animals; D055598:Chemical Phenomena; D006418:Heme / Q000737:chemistry*; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry*; D019001:Nitric Oxide Synthase / Q000737:chemistry*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D051381:Rats
D009569:Nitric Oxide; D006418:Heme; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496317:Nos2 protein, mouse; D010100:Oxygen
Biochim Biophys Acta. 1976 May 14;430(2):209-24
179587
J Biol Chem. 2005 Jan 14;280(2):965-73
15507439
Biochemistry. 2005 Apr 26;44(16):6223-31
15835910
Biochem Biophys Res Commun. 2000 Jul 21;274(1):183-7
10903916
J Inorg Biochem. 2004 Jul;98(7):1210-6
15219987
Methods Enzymol. 1996;269:41-55
8791636
Biochem Biophys Res Commun. 2006 Jun 30;345(2):704-12
16696943
J Biol Chem. 2008 May 2;283(18):12555-63
18310770
IUBMB Life. 2009 Jan;61(1):62-73
19109828
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14100-5
9826660
Drug Metab Dispos. 2001 Nov;29(11):1366-76
11602511
J Biol Chem. 1996 Dec 20;271(51):32515-8
8955074
J Biol Chem. 2000 Jun 9;275(23):17434-9
10747960
Biochemistry. 1998 Mar 17;37(11):3777-86
9521697
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7809-13
7544004
J Biol Chem. 1992 Oct 15;267(29):20547-50
1383204
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10108-12
11517313
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10378-83
9724711
J Biol Chem. 2000 Oct 13;275(41):31581-7
10922365
J Biol Chem. 1995 Sep 29;270(39):22997-3006
7559438
Biochemistry. 2000 Aug 22;39(33):10118-31
10956000
FEBS Lett. 2008 Apr 30;582(10):1395-9
18396171
J Biol Chem. 2004 Aug 27;279(35):36167-70
15133020
J Clin Invest. 1998 Feb 1;101(3):660-6
9449700
J Biol Chem. 2003 Feb 14;278(7):4919-25
12480932
Biochem J. 2001 Aug 15;358(Pt 1):201-8
11485568
J Biol Chem. 1999 Aug 27;274(35):24694-702
10455137
Nature. 2004 May 6;429(6987):79-82
15129284
J Biol Chem. 2007 May 18;282(20):14761-7
17389587
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6954-8
9192673
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):107-12
11756668
J Biol Chem. 1997 Jul 11;272(28):17349-53
9211873
FEMS Microbiol Rev. 2003 Oct;27(4):525-45
14550944
Angew Chem Int Ed Engl. 1999 Jun 14;38(12):1714-1731
29711207
J Biol Chem. 1999 May 7;274(19):13105-10
10224063
J Inorg Biochem. 2005 Jan;99(1):247-66
15598505
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1009-13
18215992
Biochemistry. 2007 Oct 23;46(42):11857-64
17900148
J Biol Chem. 2007 May 11;282(19):14101-12
17369257
Chemistry. 2004 May 3;10(9):2291-300
15112219
Biochemistry. 2004 Dec 28;43(51):16416-31
15610036
J Biol Chem. 2000 Apr 28;275(17):12581-9
10777548
Biochem J. 2001 Aug 1;357(Pt 3):593-615
11463332
J Biol Chem. 1976 May 10;251(9):2788-94
1262343
Drug Metab Rev. 2005;37(2):379-404
15931769
Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12056-61
11593016
Biochemistry. 1997 Sep 2;36(35):10609-19
9271491
J Biol Chem. 2001 Jan 12;276(2):1233-43
11038356
Biochim Biophys Acta. 1999 May 5;1411(2-3):290-309
10320664
Biochem Soc Trans. 2008 Dec;36(Pt 6):1149-54
19021514
FEBS Lett. 1998 Jul 3;430(3):377-80
9688574
J Biol Chem. 1991 Apr 5;266(10):6259-63
1706713
J Biol Chem. 2001 Dec 28;276(52):48887-98
11684690
Biochemistry. 1997 Jun 3;36(22):6814-8
9184164
J Biol Chem. 2004 May 28;279(22):22841-7
15020597
Biochim Biophys Acta. 2007 Mar;1770(3):432-45
17014963