title: CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin.
abstract: 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.
authors: Institute of Complex Systems - Molekulare Biophysik (ICS-5) Forschungszentrum Jülich, Jülich, Germany.
authors: Matteo
authors: M
authors: Gabba
authors: Stefania
authors: S
authors: Abbruzzetti
authors: Francesca
authors: F
authors: Spyrakis
authors: Flavio
authors: F
authors: Forti
authors: Stefano
authors: S
authors: Bruno
authors: Andrea
authors: A
authors: Mozzarelli
authors: F Javier
authors: FJ
authors: Luque
authors: Cristiano
authors: C
authors: Viappiani
authors: Pietro
authors: P
authors: Cozzini
authors: Marco
authors: M
authors: Nardini
authors: Francesca
authors: F
authors: Germani
authors: Martino
authors: M
authors: Bolognesi
authors: Luc
authors: L
authors: Moens
authors: Sylvia
authors: S
authors: Dewilde
mesh_terms: D001665:Binding Sites; D002248:Carbon Monoxide / Q000378:metabolism*; D018360:Crystallography, X-Ray; D000078842:Cytoglobin; D005914:Globins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D010105:Oxygenases / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D008024:Ligands; D002248:Carbon Monoxide; D005914:Globins; D010105:Oxygenases; C114415:nitric oxide dioxygenase