Carbon monoxide binding to human hemoglobin A0

Di, Enrico; Doyle, Michael L.; Connelly, Patrick R.; Gill, Stanley J.

doi:10.1021/bi00394a031

Cited by 50 publications

(31 citation statements)

References 39 publications

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“…Furthermore, we do not emphasize the complicated O 2 complexes and focus instead on complexes of CO. Notably, the CO binding by hemoglobin is also cooperative 201, 202. The electronic structure of a carbon monoxide Fe(II) porphyrin complex, [L′(porph)Fe(CO)], is rather simple, the d

_{italicz^{2}}

orbital being empty.…”

Section: The Tpe Model and σ Electronic Reorganization In Heme Chemistrymentioning

confidence: 99%

Electronic reorganization: Origin of sigma trans promotion effect

2006

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Binding of two ligands trans to each other by some transition metal complexes may be cooperative [Khoroshun et al., Mol Phys 2002, 100, 523]. Several interesting consequent effects include (i) inverse relationship between bond strength and binding affinity; (ii) smaller coordination barriers to formation of weaker bonds; (iii) enhancement of Lewis acidity with increased number of ligands. We describe a simple model, trans promotion effect (TPE), which considers electronic reorganization between two Lewis structures, and predicts the above-mentioned effects. The applied result of present study is the unified perspective on several facts of heme chemistry. Particularly, we reiterate an important but often overlooked notion, developed previously within the spin pairing model [Drago and Corden, Acc Chem Res 1980, 13, 353], that, in hemoproteins, the proximal histidine and the distal ligand such as O 2 or CO cooperate in promoting electronic reorganization. As a result, depopulation of d z 2 orbital upon ligand binding contributes to the phenomenon of hemoglobin cooperativity. The presented density functional (B3LYP) calculations on realistic models, the processes of carbon monoxide binding by Fe(II) porphyrins and dinitrogen binding by triamido/triamidoamine Mo(III) complexes, particularly the evaluation of the coordination barriers due to spin-state change by location of the minima on seams of crossing, support the TPE model predictions. From a broader theoretical perspective, the present study would hopefully stimulate the development of much needed frameworks and tools for facile comparisons of wave functions and their properties between different geometries, species, and electronic states. Advancement of practical wave function comparisons may yield fresh qualitative perspectives on chemical reactivity, and promote better understanding of related concepts such as electronic reorganization.

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_{italicz^{2}}

orbital being empty.…”

Section: The Tpe Model and σ Electronic Reorganization In Heme Chemistrymentioning

confidence: 99%

Electronic reorganization: Origin of sigma trans promotion effect

2006

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“…While the affinity of hemoglobin for oxygen increases with pH, the molecular constraints at the x p interface decrease and the intrachain H-bonds of the a chain become stronger [I]. To investigate further the effect of pH on the molecular organization of hemoglobin, the Fouriertransform infrared study of the stretching vibrations of SH was extended to the carbonmonoxy hemoglobin derivative since the partition coefficient between O2 and CO is about 260 for the fully ligated hemoglobin [7]. Furthermore, in order to obtain a more general understanding of the mechanisms correlating the proton concentration in the external solvent with the dynamic properties of these two hemoglobin forms (0, and CO), we have studied their acid/base titration behaviour and their 'H/2H exchange variations with pH.…”

mentioning

confidence: 99%

Relationship between protein/solvent proton exchange and progressive conformation and fluctuation changes in hemoglobin

Antri

Sire

Alpert

1990

European Journal of Biochemistry

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The pH dependence of the tertiary structural changes and the quaternary reorganization of the a j interface of oxyhemoglobin in solution has been previously observed in our laboratory. The present work aims to establish whether or not these progressive structural changes with pH result from proton exchange between the protein and the solvent. We therefore have used infrared spectroscopy, acidlbase titration and 'HI2H exchange to assess the effect of external proton concentration on the structural and dynamic properties of the hemoglobin molecule in solution. This study is also performed on the carbonmonoxy form since the affinity of hemoglobin for CO is much higher than for oxygen. The present findings demonstrate that affinity changes arc closely related to protein fluctuations, as well as structural modifications. An increased affinity, induced either by ligand replacement or pH variation, is associated with the constrained chains exhibiting a lower degree of fluctuation, together with a looser a/3 interface association It was recently shown that the tertiary and quaternary structures of oxyhemoglobin in solution evolve continuously with pH [l]. This gradual development was probed by observing the SH stretching vibration of two cysteinyl residues: aCysl04 (G11) and /3Cysll2 (G14). These two cysteine residues are known to be strongly H-bonded and very sensitive to slight conformational changes which are undetectable by other techniques [2, 31. The H-bond affects the distance between the sulfur and hydrogen atoms and, consequently, perturbs the SH vibration. The aCysl04 (G11) residue provides detailed information on the tertiary constraints of the G chain a-helices whereas the thiol group of pCysll2 (G14) is sensitive to quaternary structural changes at the tight ap interface Although the functional properties of hemoglobin are known to be pH dependent [5 -81, the changes in interactions inside the protein, induced by the surrounding solvent, are not yet clearly understood. While the affinity of hemoglobin for oxygen increases with pH, the molecular constraints at the x p interface decrease and the intrachain H-bonds of the a chain become stronger [I]. To investigate further the effect of pH on the molecular organization of hemoglobin, the Fouriertransform infrared study of the stretching vibrations of SH was extended to the carbonmonoxy hemoglobin derivative since the partition coefficient between O2 and CO is about 260 for the fully ligated hemoglobin [7]. Furthermore, in order to obtain a more general understanding of the mechanisms correlating the proton concentration in the external solvent with the dynamic properties of these two hemoglobin forms (0, and CO), we have studied their acid/base titration behaviour and their 'H/2H exchange variations with pH. Indeed, many protons of the protein are exchangeable with those of the external solvent [9 -121. Besides, Lumry and Rosenberg

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“…7) and brain tissues (Wiest and Steinberg 1997). This would be analogous to the biphasic binding of O 2 to hemoglobin seen in the presence of increasing partial pressure of carbon monoxide (Di Cera et al 1987). In this case, cooperative binding effects for the effector ligand (O 2 ) was shown, but in platelets binding of 3 H-BFI did not appear to be cooperative (Fig.…”

Section: Mao Activity Of Platelet Membranesmentioning

confidence: 70%

3H[2-(2-benzofuranyl)-2-imidazoline] (BFI) binding in human platelets: modulation by tranylcypromine

Wiest

Steinberg

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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2-(2-Benzofuranyl)-2-imidazoline (BFI) is a highly selective ligand for imidazoline-type 2 (I2) binding sites that are known to be associated with monoamine oxidase (MAO). Recently we demonstrated a potentiation of 3H-BFI binding in human but not in rat brain by the nonselective MAO inhibitor tranylcypromine. In the present studies, we evaluated the effect of tranylcypromine on the binding of 3H-BFI to human platelet inner membranes. Membranes were incubated with 3H-BFI at 22 degrees C in 50 mM Tris, 1.5 mM EDTA, pH 7.5. Saturation experiments with 3H-BFI (0.5-80 nM) were analyzed using non-linear curve fitting. Addition of tranylcypromine (0.1 mM) increased the number of 3H-BFI binding sites (Bmax=0.35+/-0.06 vs. 1.87+/-0.15 pmol/mg protein for vehicle and tranylcypromine, respectively) and increased 3H-BFI affinity slightly (KD =16.0+/-4.1 vs. 6.5+/-0.3 nM for vehicle and tranylcypromine, respectively). In competitive binding experiments using the less selective I2 ligand, 3H-idazoxan, tranylcypromine only weakly inhibited binding. Preincubation of platelet membranes with tranylcypromine (1 nM-10 microM) enhanced the Bmax of 3H-BFI binding in a concentration-dependent manner peaking at 1 microM (13 x control) and returning to near baseline at 100 microM. 3H-BFI binding was displaced monophasically (in order of decreasing potency) by BFI > or = 2-(4,5-dihydroimidazol-2-yl)quinoline (BU224) > or = cirazoline >idazoxan >>(1,4-benzodioxan-2-methoxy-2-yl)-2-imidazoline (RX821002)= moxonidine. Amiloride, clorgyline, guanabenz and clonidine displayed biphasic curves with nanomolar high affinity components. Tranylcypromine altered the competition curves for all ligands (except BFI) by increasing the affinities for clonidine and RX821002 and decreasing affinities for BU224, cirazoline, guanabenz, idazoxan, clorgyline, moxonidine, and amiloride. Thus, in human platelets tranylcypromine exposes a high capacity 3H-BFI binding site distinct from previously described I2 sites that retains high affintiy for BFI but not other I2 ligands. Our results suggest that 3H-BFI and 3H-idazoxan may not be considered as interchangeable probes for the I2 binding site.

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Carbon monoxide binding to human hemoglobin A0

Cited by 50 publications

References 39 publications

Electronic reorganization: Origin of sigma trans promotion effect

Electronic reorganization: Origin of sigma trans promotion effect

Relationship between protein/solvent proton exchange and progressive conformation and fluctuation changes in hemoglobin

3H[2-(2-benzofuranyl)-2-imidazoline] (BFI) binding in human platelets: modulation by tranylcypromine

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