Binding of O₂ and NO to Heme in Heme-Nitric Oxide/Oxygen-Binding (H-NOX) Proteins. A Theoretical Study

Abstract

The binding of O2 and NO to heme in Heme-Nitric Oxide/OXygen-binding (H-NOX) proteins has been investigated with DFT as well as dispersion-corrected DFT methods. The local protein environment was accounted for by including the six nearest surrounding residues in the studied systems. Attention was also paid to the effects of the protein environment, particularly the distal Tyr140, on the proximal iron–histidine (Fe–His) binding. The Heme–AB (AB = O2, NO) and Fe–His binding energies in iron porphyrin FeP(His)(AB), myoglobin Mb(AB), H-NOX( AB), and Tyr140 → Phe mutated H-NOX: Y140F(AB) were determined for comparison. The calculated stabilization of bound O2 is even higher in H-NOX than in a myoglobin (Mb), consistent with the observation that the H-NOX domain of T. tengcongensis has a very high affinity for its oxygen molecule. Among the two different X-ray crystal structures for the Tt H-NOX protein, the calculated results for both AB = O2 and NO appear to support the crystal structure with the PDB code 1XBN, where the Trp9 and Asn74 residues do not form a hydrogen bonding network with Tyr140. A hydrogen bond interaction from the polar residue does not have obvious effects on the Fe–His binding strength, but a dispersion contribution to Ebind(Fe–His) may be significant, depending on the crystal structure used. We speculate that the Fe–His binding strength in the deoxy form of a native protein could be an important factor in determining whether the bond of His to Fe is broken or maintained upon binding of NO to Fe.

A pathway for protective quenching in antenna proteins of Photosystem II

“…Different functionals (BLYP, revPBE, PW91) were tested for the calculations, but we faced several convergence or accuracy issues. The combination of the PBE Density Functional 80 , 81 in a plane-wave pseudopotential norm-conserving (NCPP) framework available in the MT (Troullier-Martins) scheme 82 and the Kleinman-Bylander approximation for the effect of core electrons 83 , proved ideal, as it is also employed elsewhere and has shown remarkable accuracy for porphyrins and chlorophylls alike 32 , 84 , 85 .…”

Heme ligation in the gas phase

“…A survey of the experimental techniques for determining the spin states of inorganic compounds is detailed in reference [40] Given the difficulty in characterizing the spin in ground state ferrous or ferric porphyrin complexes by experimental methods, quantum chemical calculations are very useful to provide reliable spin state predictions. In the last two decades, numerous theoretical reports have been devoted to this topic [10,30,[41][42][43][44]. It turns out that in the case of DFT-type calculations, the lowest spin state and the splitting between different spin components are dependent on the exchange-correlation functional and the size of the basis sets chosen [30].…”

Insights into the effect of distal histidine and water hydrogen bonding on NO ligation to ferrous and ferric heme: a DFT study

“…9 The effect of native distal group (HIS64) and other residues as a distal group into NO, has been studied experimentally and computationally by different groups. [10][11][12][13][14][15] It has been shown that the Fe II -N-O angle is bent ($140 ), while Fe III -N-O is linear ($180 ). 16 Olson et al 10 reported that ligation of NO to heme is stabilized several times using hydrogen bonding to HIS64.…”

“…As stated in previous reports on the interaction of NO to Fe-porphyrin and Mb (in absence and presence of distal His), the protein environment in Mb has slight effect on the heme-NO binding strength. 15,20,21 In this study, we have considered a simplied porphyrin-iron model to decrease the computation costs. This model has been examined in our previous work (comparing to experiment) and it has been established the model is capable enough to describe the binding of small ligands to heme.…”