Tyrosine B10 triggers a heme propionate hydrogen bonding network loop with glutamine E7 moiety

Abstract

Propionates, as peripheral groups of the heme active center in hemeproteins have been described to contribute in the modulation of heme reactivity and ligand selection. These electronic characteristics prompted the question of whether the presence of hydrogen bonding networks between propionates and distal amino acids present in the heme ligand moiety can modulate physiological relevant events, like ligand binding association and dissociation activities. Here, the role of these networks was evaluated by NMR spectroscopy using the hemoglobin I PheB10Tyr mutant from Lucina pectinata as model for TyrB10 and GlnE7 hemeproteins. 1H-NMR results for the rHbICN PheB10Tyr derivative showed chemical shifts of TyrB10 OHη at 31.00ppm, GlnE7 Nε1H/Nε2H at 10.66ppm/−3.27ppm, and PheE11 CδH at 11.75ppm, indicating the presence of a crowded, collapsed, and constrained distal pocket. Strong dipolar contacts and inter-residues crosspeaks between Gln E7/6-propionate group, GlnE7/TyrB10 and TyrB10/CN suggest that this hydrogen bonding network loop between GlnE7, TyrB10, 6-propionate group, and the heme ligand contribute significantly to the modulation of the heme iron electron density as well as the ligand stabilization mechanism. Therefore, the network loop presented here support the fact that the electron withdrawing character of the hydrogen bonding is controlled by the interaction of the propionates and the nearby electronic environments contributing to the modulation of the heme electron density state. Thus, we hypothesize that in hemeproteins with similar electrostatic environment the flexibility of the heme-6-propionate promotes a hydrogen bonding network loop between the 6-propionate, the heme ligand and nearby amino acids, tailoring in this way the electron density in the hemeligand moiety.

Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

“…The signature Arg or His residue is responsible for the hydrogen bonding with one heme propionate (Otyepka et al, 2007). It has been suggested that these hydrogen bonds not only can influence the stability of hemeproteins, but also their reactivity and ligand selection (Ramos-Santana and Lopez-Garriga, 2012). Note that Gln is also able to generate a hydrogen bond with the heme propionate.…”

Reactivity and Dynamics of H2S, NO, and O2 Interacting with Hemoglobins from Lucina pectinata

“…H 2 S Exiting the Heme Pocket and the H-Bond Network in Ferric HbI. Several side chains within the distal pocket of HbI are involved in a hydrogen bond network, 33,41 especially Gln(E7), whose mutation alters the properties of the protein. 10 The kinetic parameters of H 2 S geminate rebinding are changed upon mutation of Gln(E7) (Table 1): the proportion of H 2 S released into solution is increased for the Gln(E7)Val mutant (29%) but decreased substantially for the Gln(E7)His mutant (5%).…”

“…This six-coordinate excited species decays to the ground state with a time constant (5.8 ps) similar to that observed in the case of the O 2 sensor Dos 42 and very close to that of the truncated hemoglobin Mt-TrHbO 44 and the O 2 sensor FixL (4.7 ps), 42 for which no heme doming is observed after photoexcitation. 43 The 5.8 ps time constant, first assigned to O 2 geminate rebinding in the O 2 sensor DOS, 41 was latter reassigned to the six-coordinate vibrationally excited heme− O 2 complex on the basis of time-resolved Raman spectra, 43 a transient species that is induced by the trapping of O 2 by hydrogen bond(s) in a configuration still interacting with Fe 2+ . Consequently, only O 2 that rebinds with a τ gem of 100 ps corresponds to geminate rebinding stricto sensu, and the quantum yield for O 2 dissociation is much lower for the HbII/ III−O 2 complex than for the HbI−O 2 complex.…”