8F9I
H64A swMb-EtNO adduct
Summary for 8F9I
| Entry DOI | 10.2210/pdb8f9i/pdb |
| Descriptor | Myoglobin, PROTOPORPHYRIN IX CONTAINING FE, NITROSOETHANE, ... (5 entities in total) |
| Functional Keywords | myoglobin, nitroso, nitrosoethane, rno, mb, etno, transport protein |
| Biological source | Physeter catodon (sperm whale) |
| Total number of polymer chains | 2 |
| Total formula weight | 36235.49 |
| Authors | |
| Primary citation | Herrera, V.E.,Charles, T.P.,Scott, T.G.,Prather, K.Y.,Nguyen, N.T.,Sohl, C.D.,Thomas, L.M.,Richter-Addo, G.B. Insights into Nitrosoalkane Binding to Myoglobin Provided by Crystallography of Wild-Type and Distal Pocket Mutant Derivatives. Biochemistry, 62:1406-1419, 2023 Cited by PubMed Abstract: Nitrosoalkanes (R-N═O; R = alkyl) are biological intermediates that form from the oxidative metabolism of various amine (RNH) drugs or from the reduction of nitroorganics (RNO). RNO compounds bind to and inhibit various heme proteins. However, structural information on the resulting Fe-RNO moieties remains limited. We report the preparation of ferrous wild-type and H64A sw Mb-RNO derivatives (λ 424 nm; R = Me, Et, Pr, Pr) from the reactions of Mb-HO with dithionite and nitroalkanes. The apparent extent of formation of the wt Mb derivatives followed the order MeNO > EtNO > PrNO > PrNO, whereas the order was the opposite for the H64A derivatives. Ferricyanide oxidation of the Mb-RNO derivatives resulted in the formation of the ferric Mb-HO precursors with loss of the RNO ligands. X-ray crystal structures of the wt Mb-RNO derivatives at 1.76-2.0 Å resoln. revealed -binding of RNO to Fe and the presence of H-bonding interactions between the nitroso O-atoms and distal pocket His64. The nitroso O-atoms pointed in the general direction of the protein exterior, and the hydrophobic R groups pointed toward the protein interior. X-ray crystal structures for the H64A mutant derivatives were determined at 1.74-1.80 Å resoln. An analysis of the distal pocket amino acid surface landscape provided an explanation for the differences in ligand orientations adopted by the EtNO and PrNO ligands in their wt and H64A structures. Our results provide a good baseline for the structural analysis of RNO binding to heme proteins possessing small distal pockets. PubMed: 37011611DOI: 10.1021/acs.biochem.2c00725 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
Download full validation report
