Role of Heme Distortion on Oxygen Affinity in Heme Proteins: The Protoglobin Case

Abstract

The chemical properties of heme proteins largely reflect the electronic properties of their heme group. Often, the porphyrin ring of the heme exhibits significant distortions from its isolated structure, but the impact of these distortions on the chemical properties of the heme is yet uncertain. A systematic study focused on the effects of the distortion of the macrocycle on the binding affinity for oxygen is presented. The results show that out-of-plane distortions decrease the binding affinity, while in-plane distortions can increase or decrease it. Among in-plane distortions, only the breathing mode, which involves the symmetric compression-expansion of the porphyrin ring, strongly modulates the binding affinity. These findings shed light into the peculiar binding affinity of Methanosarcina acetivorans protoglobin, a protein that contains a highly distorted heme. Overall, the results highlight that in-plane distortions might be exploited by certain classes of heme proteins to modulate the ligand affinity.

Structural heterogeneity and ligand gating in ferric methanosarcina acetivorans protoglobin mutants

“…Phe mutants, a water ligand appears to be bound to the heme-iron, but with a coordination bond longer than expected without polar interaction(s) with heme distal site residues. Such absence of stabilizing interactions between the heme-bound ligand and distal residues strengthens the role assigned to the marked heme structural distortion on ligand affinity, as reported for O 2 binding to ferrous MaPgb (6,12). Moreover, the shape and the size of the unknown ligand found in the Tyr(B10)61 ?…”

Ligation Tunes Protein Reactivity in an Ancient Haemoglobin: Kinetic Evidence for an Allosteric Mechanism in Methanosarcina acetivorans Protoglobin

“…While showing a similar heterogeneity, the values reported here for Ma Pgb* differ from those reported previously, which were obtained for the wild type protein [6]. Recent computational analysis on the oxygenated form, suggest that the low value of the dissociation rates may be ascribed mostly to the strong distortion of the Ma Pgb* haem [33].…”

Modulation of Ligand-Field Parameters by Heme Ruffling in Cytochromes c Revealed by EPR Spectroscopy

“…In contrast with the analyses of Fe(III)-His bonding, a study of dioxygen binding to the highly distorted ferrous heme in Methanosarcina acetivorans protoglobin indicates that out-of-plane distortions decrease dioxygen affinity, whereas in-plane distortions may increase or decrease affinity. 37 Consistent with the conclusions on protoglobin, a study of the effect of heme ruffling on ligand-binding to Thermoanaerobacter tencongenesis heme nitric oxide/oxygen binding domain suggests that flattening of the heme increases the proximal bond strength of the Fe(II)-O 2 complex. 38 How ruffling affects axial ligand interactions remains a question for further research, but likely depends on heme oxidation state, electronic structure, and the nature of the ligand(s).…”