Interaction of soluble guanylate cyclase with YC-1: Kinetic and resonance Raman studies

John W. Denninger, Johannes Schelvis, Philip E. Brandish, Yunde Zhao, Gerald T. Babcock, Michael A. Marletta

Research output: Contribution to journalArticle

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Abstract

The enzyme-soluble guanylate cyclase (sGC), which converts GTP to cGMP, is a receptor for the signaling agent nitric oxide (NO). YC-1, a synthetic benzylindazole derivative, has been shown to activate sGC in an NO- independent fashion. In the presence of carbon monoxide (CO), which by itself activates sGC approximately 5-fold, YC-1 activates sGC to a level comparable to stimulation by NO alone. We have used kinetic analyses and resonance Raman spectroscopy (RR) to investigate the interaction of YC-1 and CO with guanylate cyclase. In the presence of CO and 200 μM YC-1, the V(max)/K(m GTP) increases 226-fold. While YC-1 does not perturb the RR spectrum of the ferrous form of baculovirus/Sf9 cell expressed sGC, it induces a shift in the Fe-CO stretching frequency for the CO-bound form from 474 to 492 cm-1. Similarly, YC-1 has no effect on the RR spectrum of ferrous β1(1-385), the isolated sGC heme-binding domain, but shifts the v(Fe-CO) of CO-β1(1-385) from 478 to 491 cm-1, indicating that YC-1 binds in heme-binding region of sGC. In addition, the CO-bound forms of sGC and β1(1-385) in the presence of YC-1 lie on the v(Fe-CO) vs v(C-O) correlation curve for proximal ligands with imidazole character, which suggests that histidine remains the heme proximal ligand in the presence of YC-1. Interestingly, YC-1 does not shift v(Fe-CO) for the CO-bound form of H105G(Im), the imidazole-rescued heme ligand mutant of β1(1-385). The data are consistent with binding of CO and YC-1 to the sGC heme-binding domain leading to conformational changes that give rise to an increase in catalytic turnover and a change in the electrostatic environment of the heme pocket.

Original languageEnglish
Pages (from-to)4191-4198
Number of pages8
JournalBiochemistry
Volume39
Issue number14
DOIs
StatePublished - 11 Apr 2000

Fingerprint

Guanylate Cyclase
Carbon Monoxide
Kinetics
Heme
Raman Spectrum Analysis
Raman spectroscopy
Nitric Oxide
Ligands
Guanosine Triphosphate
Soluble Guanylyl Cyclase
Sf9 Cells
Baculoviridae
Static Electricity
Histidine
Stretching
Electrostatics

Cite this

Denninger, J. W., Schelvis, J., Brandish, P. E., Zhao, Y., Babcock, G. T., & Marletta, M. A. (2000). Interaction of soluble guanylate cyclase with YC-1: Kinetic and resonance Raman studies. Biochemistry, 39(14), 4191-4198. https://doi.org/10.1021/bi992332q
Denninger, John W. ; Schelvis, Johannes ; Brandish, Philip E. ; Zhao, Yunde ; Babcock, Gerald T. ; Marletta, Michael A. / Interaction of soluble guanylate cyclase with YC-1 : Kinetic and resonance Raman studies. In: Biochemistry. 2000 ; Vol. 39, No. 14. pp. 4191-4198.
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Denninger, JW, Schelvis, J, Brandish, PE, Zhao, Y, Babcock, GT & Marletta, MA 2000, 'Interaction of soluble guanylate cyclase with YC-1: Kinetic and resonance Raman studies', Biochemistry, vol. 39, no. 14, pp. 4191-4198. https://doi.org/10.1021/bi992332q

Interaction of soluble guanylate cyclase with YC-1 : Kinetic and resonance Raman studies. / Denninger, John W.; Schelvis, Johannes; Brandish, Philip E.; Zhao, Yunde; Babcock, Gerald T.; Marletta, Michael A.

In: Biochemistry, Vol. 39, No. 14, 11.04.2000, p. 4191-4198.

Research output: Contribution to journalArticle

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T1 - Interaction of soluble guanylate cyclase with YC-1

T2 - Kinetic and resonance Raman studies

AU - Denninger, John W.

AU - Schelvis, Johannes

AU - Brandish, Philip E.

AU - Zhao, Yunde

AU - Babcock, Gerald T.

AU - Marletta, Michael A.

PY - 2000/4/11

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N2 - The enzyme-soluble guanylate cyclase (sGC), which converts GTP to cGMP, is a receptor for the signaling agent nitric oxide (NO). YC-1, a synthetic benzylindazole derivative, has been shown to activate sGC in an NO- independent fashion. In the presence of carbon monoxide (CO), which by itself activates sGC approximately 5-fold, YC-1 activates sGC to a level comparable to stimulation by NO alone. We have used kinetic analyses and resonance Raman spectroscopy (RR) to investigate the interaction of YC-1 and CO with guanylate cyclase. In the presence of CO and 200 μM YC-1, the V(max)/K(m GTP) increases 226-fold. While YC-1 does not perturb the RR spectrum of the ferrous form of baculovirus/Sf9 cell expressed sGC, it induces a shift in the Fe-CO stretching frequency for the CO-bound form from 474 to 492 cm-1. Similarly, YC-1 has no effect on the RR spectrum of ferrous β1(1-385), the isolated sGC heme-binding domain, but shifts the v(Fe-CO) of CO-β1(1-385) from 478 to 491 cm-1, indicating that YC-1 binds in heme-binding region of sGC. In addition, the CO-bound forms of sGC and β1(1-385) in the presence of YC-1 lie on the v(Fe-CO) vs v(C-O) correlation curve for proximal ligands with imidazole character, which suggests that histidine remains the heme proximal ligand in the presence of YC-1. Interestingly, YC-1 does not shift v(Fe-CO) for the CO-bound form of H105G(Im), the imidazole-rescued heme ligand mutant of β1(1-385). The data are consistent with binding of CO and YC-1 to the sGC heme-binding domain leading to conformational changes that give rise to an increase in catalytic turnover and a change in the electrostatic environment of the heme pocket.

AB - The enzyme-soluble guanylate cyclase (sGC), which converts GTP to cGMP, is a receptor for the signaling agent nitric oxide (NO). YC-1, a synthetic benzylindazole derivative, has been shown to activate sGC in an NO- independent fashion. In the presence of carbon monoxide (CO), which by itself activates sGC approximately 5-fold, YC-1 activates sGC to a level comparable to stimulation by NO alone. We have used kinetic analyses and resonance Raman spectroscopy (RR) to investigate the interaction of YC-1 and CO with guanylate cyclase. In the presence of CO and 200 μM YC-1, the V(max)/K(m GTP) increases 226-fold. While YC-1 does not perturb the RR spectrum of the ferrous form of baculovirus/Sf9 cell expressed sGC, it induces a shift in the Fe-CO stretching frequency for the CO-bound form from 474 to 492 cm-1. Similarly, YC-1 has no effect on the RR spectrum of ferrous β1(1-385), the isolated sGC heme-binding domain, but shifts the v(Fe-CO) of CO-β1(1-385) from 478 to 491 cm-1, indicating that YC-1 binds in heme-binding region of sGC. In addition, the CO-bound forms of sGC and β1(1-385) in the presence of YC-1 lie on the v(Fe-CO) vs v(C-O) correlation curve for proximal ligands with imidazole character, which suggests that histidine remains the heme proximal ligand in the presence of YC-1. Interestingly, YC-1 does not shift v(Fe-CO) for the CO-bound form of H105G(Im), the imidazole-rescued heme ligand mutant of β1(1-385). The data are consistent with binding of CO and YC-1 to the sGC heme-binding domain leading to conformational changes that give rise to an increase in catalytic turnover and a change in the electrostatic environment of the heme pocket.

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