NMR and crystallographic structural studies of the extremely stable monomeric variant of human cystatin C with single amino acid substitution.

摘要: Human cystatin C (hCC), a member of the superfamily papain-like cysteine protease inhibitors, is most widespread in human body fluids. This small protein, addition to its physiological function, involved various diseases, including cerebral amyloid angiopathy, hemorrhage, stroke, and dementia. Physiologically active hCC monomer. However, all structural studies based on crystallization led dimeric structure formed as result three-dimensional exchange protein domains (3D domain swapping). The monomeric was obtained only for variant V57N stabilized by an additional disulfide bridge. With this study, we extend number models with single amino acid substitution flexible loop L1. V57G chosen X-ray NMR analysis due exceptional conformational stability solution. In work, show first time dynamics We were also able compare these data crystal other cystatins. overall fold retained solute form. Additionally, information concerning N terminus during our presented time. DATABASE: Crystallographic structure: are available PDB databases under accession 6ROA. BMRB numbers 6RPV 34399, respectively.