HNO Binding in a Heme Protein: Structures, Spectroscopic Properties, and Stabilities

Abstract

HNO can interact with numerous heme proteins, but atomic level structures are largely unknown. In this work, various structural models for the first stable HNO heme protein complex, MbHNO (Mb, myoglobin), were examined by quantum chemical calculations. This investigation led to the discovery of two novel structural models that can excellently reproduce numerous experimental spectroscopic properties. They are also the first atomic level structures that can account for the experimentally observed high stabilities. These two models involve two distal His conformations as reported previously for MbCNR and MbNO. However, a unique dual hydrogen bonding feature of the HNO binding was not reported before in heme protein complexes with other small molecules such as CO, NO, and O2. These results shall facilitate investigations of HNO bindings in other heme proteins.

Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases

“…All models were subject to partial geometry optimizations with only protein residue Cα atoms fixed at the X-ray structure positions to mimic the protein environment, based on the previous work. 50 In the initial setup for Zn-Fe B Mb-O 2 , heme iron and O 2 moiety are of Fe III (S=1/2) anti-ferromagnetically coupled with O 2 − (S= −1/2). In case where the second metal is Fe and Cu, the initial set up of non-heme site metal is in its oxidized state (i.e.…”

Computational investigations of HNO in biology

“…NO − ) was reported with the assistance of a specially designed porphyrin [59], and there is still no report of a successful synthesis of iron porphyrin HNO complex. In contrast, most reported HNO metalloprotein systems are with Fe [1–3,15–18] and the protein environment was found to help stabilize the HNO binding in myoglobin (Mb) [60]. These results suggest that the early transition metal may bind with HNO more weakly than the late transition metal, and thus needs the aid of a special ligand or protein environment.…”

“…Apart from the above computational investigations that assisted in understanding the experimental spectroscopic properties of HNO metal complexes and related characterization of HNO binding in some heme and non-heme metal systems, accurate computational calculations of some characteristic spectroscopic properties have also helped in the discovery of a unique HNO binding mode in the first stable HNO protein complex—MbHNO [60], as with previous integrated quantum mechanics and spectroscopic studies of protein structures [44,69–74]. For a number of NO/HNO/RNO (R = alkyl and aryl) containing systems, our DFT predictions of the 1 H and 15 N NMR shifts and NO vibrational frequencies have theory-versus-experiment correlation coefficients R 2 =0.990, 0.996, and 0.998 respectively, with errors being 1.8–3.1% of the experimental data ranges [29].…”

Iron Binding Site in a Global Regulator in Bacteria–Ferric Uptake Regulator (Fur) Protein: Structure, Mössbauer Properties, and Functional Implication

“…To more rigorously evaluate these site 1 and site 2 models, a reduced χ 2 analysis and Bayesian probability (or Z-surface) technique 37 were employed, using both experimental Mössbauer isomer shift and quadrupole splitting (see Supporting Information for details). A small χ 2 value indicates a small deviation from experiment and a large Z value means a high probability of the model corresponding to the experimental system.…”