Nitrosyl Myoglobins and Their Nitrite Precursors: Crystal Structural and QM/MM Theoretical Investigations into Preferred Fe–NO Ligand Orientations in Myoglobin Distal Pockets

The globular dioxygen-binding heme protein myoglobin (Mb) is present in several species. Its interactions with the simple nitrogen oxides, namely nitric oxide (NO) and nitrite, have been known for decades, but the physiological relevance has only recently become more fully appreciated. We previously...

Full description

Bibliographic Details
Published in:Biochemistry
Main Authors: Wang, Bing, Shi, Yelu, Tejero, Jesús, Powell, Samantha M., Thomas, Leonard M., Gladwin, Mark T., Shiva, Sruti, Zhang, Yong, Richter-Addo, George B.
Format: Text
Language:English
Published: 2018
Subjects:
Article
Sperm whale
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474360/
http://www.ncbi.nlm.nih.gov/pubmed/29999305
https://doi.org/10.1021/acs.biochem.8b00542
Description
Summary:The globular dioxygen-binding heme protein myoglobin (Mb) is present in several species. Its interactions with the simple nitrogen oxides, namely nitric oxide (NO) and nitrite, have been known for decades, but the physiological relevance has only recently become more fully appreciated. We previously reported the O-nitrito binding mode of nitrite to ferric horse heart wild-type (wt) Mb(III) and human hemoglobin. We have expanded on this work and report the interactions of nitrite with wt sperm whale (sw) Mb(III) and its H64A, H64Q and V68A/I107Y mutants whose dissociation constants increase in the order H64Q < wt < V68A/I107Y < H64A. We also report their X-ray crystal structures that reveal the O-nitrito binding mode of nitrite to these derivatives. The Mb(II)-mediated reductions of nitrite to NO and structural data for the wt and mutant Mb(II)–NOs are described. We show that their FeNO orientations vary with distal pocket identity, with the FeNO moieties pointing towards the hydrophobic interiors when the His64 residue is present, but pointing towards the hydrophilic exterior in the absence of this His64 residue. This correlates with the nature of H-bonding to the bound NO ligand (nitrosyl O vs. N atom). Quantum mechanics and hybrid quantum mechanics/molecular mechanics calculations help elucidate the origin of the experimentally preferred NO orientations. In a few cases, the calculations reproduce the experimentally observed orientations only when the whole protein is taken into consideration.

Similar Items