Characterization of Nitrosoalkane Binding and Activation of Soluble Guanylate Cyclase

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• 作者：Emily R. Derbyshire ; Rosalie Tran ; Richard A. Mathies ; and Michael A. Marletta
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：December 13, 2005
• 年：2005
• 卷：44
• 期：49
• 页码：16257 - 16265
• 全文大小：119K
• 年卷期：v.44,no.49(December 13, 2005)
• ISSN：1520-4995

文摘

Soluble guanylate cyclase (sGC) is the primary receptor for the signaling agent nitric oxide(NO). Electronic absorption and resonance Raman spectroscopy were used to show that nitrosoalkanesbind to the heme of sGC to form six-coordinate, low-spin complexes. In the sGC-nitrosopentane complex,a band assigned to an Fe-N stretching vibration is observed at 543 cm^-1 which is similar to valuesreported for other six-coordinate NO-bound hemoproteins. Nitrosoalkanes activate sGC 2-6-fold andsynergize with YC-1, a synthetic benzylindazole derivative, to activate the enzyme 11-47-fold. In addition,the observed off-rates of nitrosoalkanes from sGC were found to be dependent on the alkyl chain length.A linear correlation was found between the observed off-rates and the alkyl chain length which suggeststhat the sGC heme has a large hydrophobic distal ligand-binding pocket. Together, these data show thatnitrosoalkanes are a novel class of heme-based sGC activators and suggest that heme ligation is a generalrequirement for YC-1 synergism.