2026-04-17T13:51:10Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1278492025-12-05T14:55:25Zcom_2072_1057col_2072_478917col_2072_478924

00925njm 22002777a 4500 dc Gabba, Matteo author Abbruzzetti, Stefania author Spyrakis, Francesca author Forti, Flavio author Bruno, Stefano author Mozzarelli, Andrea author Luque Garriga, F. Xavier author Viappiani, Cristiano author Cozzini, Pietro author Nardini, Marco author Germani, Francesca author Bolognesi, Martino author Moens, Luc author Dewilde, Sylvia author 2019-02-04T12:40:52Z 2019-02-04T12:40:52Z 2013-01-04 2019-02-04T12:40:52Z Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation) of a bis-histidyl heme hexacoordinated reaction intermediate. Ligand exit to the solvent occurs through distinct pathways, some of which exploit temporary docking sites. The remarkable change in energetic barriers, linked to heme bis-histidyl hexacoordination by HisE7, may be responsible for active regulation of the flux of reactants and products to and from the reaction site on the distal side of the heme. A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state. These findings are consistent with the expected versatility of the molecular activity of this protein. Bioquímica Biologia molecular Genètica Metabolisme Cinètica enzimàtica Biochemistry Molecular biology Genetics Metabolism Enzyme kinetics CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin