Variable forms of soluble guanylyl cyclase: protein-ligand interactions and the issue of activation by carbon monoxide

Vogel, Kathleen M.; Hu, Songzhou; Spiro, Thomas G.; Dierks, Elizabeth A.; Yu, Anita E.; Burstyn, Judith N.

doi:10.1007/s007750050354

Cited by 48 publications

(68 citation statements)

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“…2) suggests that the calculation provides a reliable guide to the character of the individual modes. This includes observed features at 507 cm -1 , 561 cm -1 , and 586 cm -1 ,associated with Fe-CO stretching and FeCO bending, as previously seen in numerous heme proteins [50][51][52][53][54][55][56][57][58][59][60]. A more detailed description of these modes, together with measurements on related compounds, will appear elsewhere.…”

Section: One-quantum Transitionsmentioning

confidence: 62%

Vibrational dynamics of biological molecules: Multi-quantum contributions

Leu

Zgierski

Wyllie

et al. 2005

Journal of Physics and Chemistry of Solids

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High-resolution X-ray measurements near a nuclear resonance reveal the complete vibrational spectrum of the probe nucleus. Because of this, nuclear resonance vibrational spectroscopy (NRVS) is a uniquely quantitative probe of the vibrational dynamics of reactive iron sites in proteins and other complex molecules. Our measurements of vibrational fundamentals have revealed both frequencies and amplitudes of 57 Fe vibrations in proteins and model compounds. Information on the direction of Fe motion has also been obtained from measurements on oriented single crystals, and provides an essential test of normal mode predictions. Here, we report the observation of weaker two-quantum vibrational excitations (overtones and combinations) for compounds that mimic the active site of heme proteins. The predicted intensities depend strongly on the direction of Fe motion. We compare the observed features with predictions based on the observed fundamentals, using information on the direction of Fe motion obtained either from DFT predictions or from single crystal measurements. Two-quantum excitations may become a useful tool to identify the directions of the Fe oscillations when single crystals are not available.

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Section: One-quantum Transitionsmentioning

confidence: 62%

Vibrational dynamics of biological molecules: Multi-quantum contributions

Leu

Zgierski

Wyllie

et al. 2005

Journal of Physics and Chemistry of Solids

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“…One of these is reconstituted sGC (labeled sGC 1 in Figure 4), in which heme is added back to protein that has lost heme during isolation (41). The νFeC/νCO point for sGC 1 is close to that of Mb(H64L), suggesting that the reconstitution did not establish the strong propionate H-bonds of the native protein (although it did support activation by NO (41)).…”

Section: H-nox: Propionate H-bonding Porphyrin Distortion and Stericmentioning

confidence: 99%

DFT Analysis of Axial and Equatorial Effects on Heme−CO Vibrational Modes: Applications to CooA and H−NOX Heme Sensor Proteins

Ibrahim

Spiro

2008

Biochemistry

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Determinants of the Fe-CO and C-O stretching frequencies in (imidazole) heme-CO adducts have been investigated via Density Functional Theory (DFT) analysis, in connection with puzzling characteristics of the heme sensor protein CooA, and of the H-NOX (Heme-Nitric Oxide and/or OXygen binding) family of proteins, including soluble guanylate cyclase (sGC). The computations show that two mechanisms of Fe-histidine bond weakening have opposite effects on the νFeC/νCO pattern. Mechanical tension is expected to raise νFeC with little change in νCO, while weakening of H-bond donation from the imidazole ligand has the opposite effect. Data on CooA indicate imidazole H-bond weakening associated with heme displacement, as part of the activation mechanism. The computations also reveal that protein-induced distortion of the porphyrin ring, a prominent structural feature of the H-NOX protein TtTar4H (Thermoanaerobacter tengcongensis Tar4 protein), has surprisingly little effect on νFeC or νCO. However, another structural feature, strong H-bonding to the propionates, is suggested to account for the weakened backbonding that is evident in sGC. TtTar4H-CO itself has an elevated νFeC, which is successfully modeled as a compression effect, resulting from steric crowding in the distal pocket. νFeC/νCO data, in conjunction with modeling, can provide valuable insight into mechanisms for heme-protein modulation.

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“…Raman spectra are shown in Figures 3 and 4 (β1(1-194) and β2(1-217), respectively) and the data summarized in Tables 2, 3 and 4 (Fe +2 -unligated, CO adducts and NO adducts, respectively) along with comparisons to sGC (16,17), Mb (18)(19)(20)(21)(22)(23), Acetobacter xylinum PDEA1H (the heme domain of AxPDEA1) (24), rat sGC β1(1-385) (25), FixLN (the heme domain of FixL) (26), Alcaligenes xylosoxidans cyt c' (27,28), HemAT-Bs (29), and CooA (30). Specific complexes are described below.…”

Section: Resonance Raman Spectroscopymentioning

confidence: 99%

Characterization of Functional Heme Domains from Soluble Guanylate Cyclase

et al. 2005

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Soluble guanylate cyclase (sGC) is a heterodimeric, nitric oxide (NO)-sensing hemoprotein composed of two subunits, α1 and β1. NO binds to the heme cofactor in the β1 subunit, forming a 5-coordinate NO complex that activates the enzyme several hundred-fold. In this report the heme domain has been localized to the N-terminal 194 residues of the β1 subunit. This fragment represents the smallest construct of the β1 subunit that retains the ligand binding characteristics of the native enzyme, namely tight affinity for NO and no observable binding of O 2 . A functional heme domain from the rat β2 subunit has been localized to the first 217 amino acids β2(1-217). These proteins are ∼40% identical to the rat β1 heme domain, form 5-coordinate, low-spin NO complexes and 6-coordinate, low-spin CO complexes. Like sGC these constructs have a weak Fe-His stretch (208 and 207 cm −1 for β1 and β2(1-217), respectively). β2(1-217) forms a CO complex that is very similar to sGCand has a high ν(CO) stretching frequency at 1994 cm −1 . The autoxidation rate of β1 (1-194) was 0.073 per minute, while the β2(1-217) was substantially more stable in the ferrous form with an autoxidation rate of 0.003 per minute at 37 °C. This report has identified and characterized the minimum functional ligand binding heme domain derived from sGC providing key details towards a comprehensive characterization.Soluble guanylate cyclase (sGC 1 ) is a well-characterized NO-sensor, containing a hemebound, N-terminal domain that binds NO, regulating a C-terminal guanylate cyclase. sGC catalyzes the conversion of GTP to cGMP, and it is a heterodimer, composed of α1 and β1 subunits. The ferrous heme is ligated to the β1 subunit via H105 (1), and when NO is bound, the activity of the enzyme is 300-fold elevated over basal activity (2). sGC has evolved to selectively bind NO and not O 2 . It does not form a stable, isolable complex with O 2 , permitting NO to bind selectively to the Fe +2 heme in an aerobic environment. This selectivity is essential Δ This work was supported in part by LDRD fund of the Lawrence Berkeley National Laboratory ‡ Present address: Pacific Northwest National Laboratory, K8-88 Richland, WA 99352. * To whom correspondence should be addressed: University of California, Berkeley, Department of Chemistry, Berkeley, CA, 94720-1460. Telephone: 510-643-9325. Fax: 510-643-9388. E-mail: marletta@berkeley.edu 1 Abbreviations: CO, carbon monoxide; sGC, soluble guanylate cyclase; NO, nitric oxide; TtTar4H, N-terminal 188 amino acids of Thermoanaerobacter tengcongensis Tar4 (heme domain); MCP, methyl-accepting chemotaxis protein; AxPDEA1H, Acetobacter xylinum phosphodiesterase A1 heme domain; Mb, myoglobin; H-NOX domain, Heme-Nitric oxide/OXygen binding domain. sGC has been characterized in animals ranging from Drosophila to humans and, until recently, there had been no reports of any other NO sensors except for sGC. Notably, no heme-containing NO sensors had been found in prokaryotes, which could be exposed to both exogenous and endogenou...

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Variable forms of soluble guanylyl cyclase: protein-ligand interactions and the issue of activation by carbon monoxide

Cited by 48 publications

References 0 publications

Vibrational dynamics of biological molecules: Multi-quantum contributions

Vibrational dynamics of biological molecules: Multi-quantum contributions

DFT Analysis of Axial and Equatorial Effects on Heme−CO Vibrational Modes: Applications to CooA and H−NOX Heme Sensor Proteins

Characterization of Functional Heme Domains from Soluble Guanylate Cyclase

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