Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations

Amrita Roy; Liangzhong Lim; Shagun Srivastava; Jianxing Song

Here, we have successfully obtained both linked and unlinked Zika NS2B-NS3pro complexes, which, despite sharing similarity, do have some unique catalytic features including the lower substrate affinity but higher efficiency than those of the complexes of all four Dengue serotypes. Most strikingly, as reported by CD and NMR HSQC spectroscopy, Zika NS2B appears to be much more dynamic and disordered than Dengue NS2B of the same length as we previously studied (12) . Indeed, in preparation of our current manuscript, a crystal structure was published on Zika NS2B-NS3pro which was linked with (Gly)4-Ser-(Gly)4 but had almost all flexible regions of both NS2B and NS3pro deleted (25) . Interestingly, it was reported that unlike Dengue complexes whose high-quality crystals could be obtained for the "open" form, this small Zika complex could only be crystallized in complex with a tight competitive inhibitor, and consequently the structure represents a "closed" form ( Fig. 6) , in which the characteristic author/funder. All rights reserved. No reuse allowed without permission.