title: Soluble guanylate cyclase is activated differently by excess NO and by YC-1: resonance Raman spectroscopic evidence.
abstract: Modulation of soluble guanylate cyclase (sGC) activity by nitric oxide (NO) involves two distinct steps. Low-level activation of sGC is achieved by the stoichiometric binding of NO (1-NO) to the heme cofactor, while much higher activation is achieved by the binding of additional NO (xsNO) at a non-heme site. Addition of the allosteric activator YC-1 to the 1-NO form leads to activity comparable to that of the xsNO state. In this study, the mechanisms of sGC activation were investigated using electronic absorption and resonance Raman (RR) spectroscopic methods. RR spectroscopy confirmed that the 1-NO form contains five-coordinate NO-heme and showed that the addition of NO to the 1-NO form has no significant effect on the spectrum. In contrast, addition of YC-1 to either the 1-NO or xsNO forms alters the RR spectrum significantly, indicating a protein-induced change in the heme geometry. This change in the heme geometry was also observed when BAY 41-2272 was added to the xsNO form. Bands assigned to bending and stretching motions of the vinyl and propionate substituents undergo changes in intensity in a pattern suggesting altered tilting of the pyrrole rings to which they are attached. In addition, the N-O stretching frequency increases, with no change in the Fe-NO stretching frequency, an effect modeled via DFT calculations as resulting from a small opening of the Fe-N-O angle. These spectral differences demonstrate different mechanisms of activation by synthetic activators, such as YC-1 and BAY 41-2272, and excess NO.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Emily R
authors.initials: ER
authors.lastname: Derbyshire
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Soldatova
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Spiro
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D018360:Crystallography, X-Ray; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology*; D009569:Nitric Oxide / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman
chemical_list: D020536:Enzyme Activators; D007191:Indazoles; D018160:Receptors, Cytoplasmic and Nuclear; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
references.citation: Nat Chem Biol. 2005 Jun;1(1):53-9
references.pmid: 16407994
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21602-7
references.pmid: 20007374
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12854-9
references.pmid: 15326296
references.citation: Biochemistry. 2008 Mar 25;47(12):3892-9
references.pmid: 18302323
references.citation: Handb Exp Pharmacol. 2009;(191):277-308
references.pmid: 19089334
references.citation: Biochemistry. 1996 Apr 16;35(15):4939-44
references.pmid: 8664286
references.citation: Biochemistry. 1997 Aug 19;36(33):10155-60
references.pmid: 9254612
references.citation: J Biol Chem. 2003 Mar 28;278(13):11130-7
references.pmid: 12540839
references.citation: Biochemistry. 2005 Jan 25;44(3):939-46
references.pmid: 15654750
references.citation: Biochemistry. 1997 Dec 16;36(50):15959-64
references.pmid: 9398330
references.citation: Front Biosci. 2003 Jan 01;8:d264-78
references.pmid: 12456375
references.citation: Bioorg Med Chem Lett. 2001 Mar 26;11(6):781-4
references.pmid: 11277519
references.citation: Handb Exp Pharmacol. 2009;(191):1-14
references.pmid: 19089322
references.citation: Biochemistry. 2003 May 6;42(17):4896-903
references.pmid: 12718530
references.citation: EMBO J. 2007 Jan 24;26(2):578-88
references.pmid: 17215864
references.citation: J Biomed Biotechnol. 2004;2004(4):227-237
references.pmid: 15467163
references.citation: Blood. 1994 Dec 15;84(12):4226-33
references.pmid: 7527671
references.citation: J Am Chem Soc. 2006 Dec 27;128(51):16834-45
references.pmid: 17177434
references.citation: Handb Exp Pharmacol. 2009;(191):17-31
references.pmid: 19089323
references.citation: Biochemistry. 1996 Feb 6;35(5):1540-7
references.pmid: 8634285
references.citation: Biochemistry. 2010 May 11;49(18):3815-23
references.pmid: 20353168
references.citation: Biochemistry. 1996 Jan 30;35(4):1093-9
references.pmid: 8573563
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19753-60
references.pmid: 19918063
references.citation: Biochemistry. 1998 Sep 8;37(36):12431-42
references.pmid: 9730815
references.citation: J Phys Chem A. 2007 Nov 15;111(45):11683-700
references.pmid: 17948971
references.citation: Biochemistry. 1998 Nov 17;37(46):16289-97
references.pmid: 9819221
references.citation: ACS Chem Biol. 2008 Nov 21;3(11):703-10
references.pmid: 19032091
references.citation: Biochemistry. 2009 Sep 15;48(36):8568-77
references.pmid: 19653642
references.citation: Curr Opin Chem Biol. 2005 Oct;9(5):441-6
references.pmid: 16125437
references.citation: J Inorg Biochem. 2005 Jan;99(1):267-79
references.pmid: 15598506
references.citation: Biochemistry. 2005 Dec 13;44(49):16266-74
references.pmid: 16331987
references.citation: Trends Biochem Sci. 2006 Apr;31(4):231-9
references.pmid: 16530415
references.citation: Science. 2004 Nov 26;306(5701):1550-3
references.pmid: 15472039
references.citation: Nature. 2001 Mar 8;410(6825):212-5
references.pmid: 11242081
references.citation: Biochemistry. 2000 Apr 11;39(14):4191-8
references.pmid: 10747811
references.citation: J Am Chem Soc. 2005 Apr 6;127(13):4625-31
references.pmid: 15796527
references.citation: Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2592-6
references.pmid: 7908439
references.citation: J Biol Chem. 2007 Jan 12;282(2):897-907
references.pmid: 17098738
references.citation: Biochemistry. 2000 Jul 18;39(28):8234-42
references.pmid: 10889031
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13064-9
references.pmid: 16131543
references.citation: EMBO J. 2004 Nov 10;23(22):4443-50
references.pmid: 15510222