<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Penta-L-lysine Potentiates Fibrin-Independent Activity of Human Tissue Plasminogen Activator."^^ . "The therapeutic action of tissue plasminogen activator (t-PA) is a two-step process: (1) binding to lysine-rich fibrin (Km event) and (2) converting local plasminogen into plasmin (Kcat event). Overcoming limitations of other structural biophysics methods, we wanted to employ small-angle X-ray scattering (SAXS) to visualize what shape changes occur/accompany t-PA activation, but the prime hurdle was the polydisperse nature of the fibrin, which occluded scattering information from t-PA. Earlier, larger polylysine peptides have been used to potentiate activation of t-PA, so while screening short polylysine peptides as alternatives to fibrin or larger peptides, we found that penta-polylysine (P5) specifically activates t-PA in a dose-dependent manner, averaging to almost 3-fold more than in the absence of any peptide. SAXS data analysis confirmed that P5 does not induce association of t-PA molecules, and a narrower peak profile of the Kratky plot indicated that P5 binding quenches inherent motion in t-PA. Shape reconstruction of t-PA ∓ P5 revealed that P5 closes the \"gap\" between the two gross domains of t-PA, viz. fused F/E, K1 and K2 domains, and the P domain. Docking experiments suggested that, while other polylysine peptides preferentially interacted with the surfaces of kringle domains, P5 \"slipped into\" the gap/groove between K2 and P domains, thereby mediating a substantial increase in the number of long-range interactions between the K2 domain and exosites in the P domain. We report here dissection of shape events involved in between Km/Kcat steps of t-PA activation, which can pave the way toward the search for small molecule function regulator(s) of t-PA."^^ . "2015-10-22" . "119" . "42" . . "ACS Publications"^^ . . . "The journal of physical chemistry. B"^^ . . . "15205207" . . . . . . . . . . . . . . . . . . . . . . "Sanskruti"^^ . "Mishra"^^ . "Sanskruti Mishra"^^ . . "Ashish"^^ . "Ganguly"^^ . "Ashish Ganguly"^^ . . "Amin"^^ . "Sagar"^^ . "Amin Sagar"^^ . . "Vandna"^^ . "Sharma"^^ . "Vandna Sharma"^^ . . "Girish"^^ . "Sahni"^^ . "Girish Sahni"^^ . . "Mohammad"^^ . "Rehan"^^ . "Mohammad Rehan"^^ . . . . . "HTML Summary of #1749 \n\nPenta-L-lysine Potentiates Fibrin-Independent Activity of Human Tissue Plasminogen Activator.\n\n" . "text/html" . . . "QR Microbiology"@en . .