Specificity profiling, activity in human plasma, and x-ray structure

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Fig. 4 Specificity profiling, activity in human plasma, and x-ray structure. Specificity profiling, activity in human plasma, and x-ray structure. (A) Inhibition of homologous proteases by P2. APC, activated protein C; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator; PK, plasma kallikrein. (B) Inhibition of coagulation in human blood plasma. (C) X-ray structure of P2 bound to thrombin at a resolution of 2.3 Å (PDB entry 6GWE). The 60 and γ-loops are shown for orientation. Colors correspond to those in Fig. 3C. (D) Binding to non-prime subsites S1, S2, S4, and a new cavity. H-bond interactions are shown as green dashed lines. (E) Non-prime site of thrombin without P2 bound (PDB 1SG8). (F) Side chain of Glu217 before (blue; from thrombin structures ASG8, 4HFP, and 1HGT) and after P2 binding (orange). Linker 2 of P2 is shown in the figure. S. S. Kale et al. Sci Adv 2019;5:eaaw2851 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).