Atomistic Simulations of Heme Dissociation Pathways in Human Methemoglobins Reveal Hidden Intermediates.

ABSTRACT: Heme dissociations disrupt function and structural integrity of human hemoglobin and trigger various cardiovascular complications. These events become significant in methemoglobins that have undergone autoxidation of ferrous into ferric heme. We have structurally characterized the heme disassociation pathways for adult tetrameric methemoglobins using all-atom molecular dynamics simulations. These reveal that bis-histidine hemichromes, characterized here by the coordination of heme iron to both the F8 (proximal) and E7 (distal) histidines, are seen as intermediates following dissociation of the water molecule distally bound to each heme iron. Later, the breaking of coordination between heme iron and proximal histidine disrupts the F helix and pushes it away from the heme cavity, enabling bo

SUBMITTER: Samuel PP 

PROVIDER: S-EPMC8088502 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature