Molecular Mechanism for the Regulation of Rho-Kinase by Dimerization and Its Inhibition by Fasudil

SummaryRho-kinase is a key regulator of cytoskeletal events and a promising drug target in the treatment of vascular diseases and neurological disorders. Unlike other protein kinases, Rho-kinase requires both N- and C-terminal extension segments outside the kinase domain for activity, although the details of this requirement have been elusive. The crystal structure of an active Rho-kinase fragment containing the kinase domain and both the extensions revealed a head-to-head homodimer through the N-terminal extension forming a helix bundle that structurally integrates the C-terminal extension. This structural organization enables binding of the C-terminal hydrophobic motif to the N-terminal lobe, which defines the correct disposition of helix αC that is important for the catalytic activity. The bound inhibitor fasudil significantly alters the conformation and, consequently, the mode of interaction with the catalytic cleft that contains local structural changes. Thus, both kinase and drug conformational pliability and stability confer selectivity

Observation of the thermosiphon effect in the circulation of liquid nitrogen in HTS cable cooling system

AbstractIt is traditionally considered that superconducting technology is just the way that will help to overcome the energy crisis and improve the environmental safety of the electricity production. However, real achievements in this field still insufficient to build commercial long power transmission lines. In particular, cooling systems constructed using expensive coolant circulation pumps have to be improved. Our previous calculations show that the use of a thermosiphon effect may reduce both the heat load and the required coolant circulation pump power and, ideally, would completely abandon the forced circulation. Direct experimental verification of this approach has been carried out at the new 200-meter HTS DC experimental facility of the Chubu University. The thermosiphon effect was clearly observed in satisfactory agreement with theory, although the change in elevation of the cryopipe was small. Our results will be used to design an effective HTS cable cooling system based on natural circulation of the coolant