NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin α 1 β 1

NMR analysis of four recombinant jerdostatin molecules was assessed to define the structural basis of two naturally occurring gain‐of‐function events: C‐terminal dipeptide processing and mutation of the active residue K21 to arginine. Removal of the highly mobile and a bulky C‐terminal dipeptide produced pronounced chemical shift changes in the sequentially unconnected but spatially nearby α 1 β 1 inhibitory loop. Analysis of chemical shift divergence and 15 N backbone relaxation dynamics indicated differences in motions in the picosecond to nanosecond time scale, and the higher T 2 rate of S25, S26, and H27 of rJerK21 point to a slowdown in the microsecond to millisecond motions of these residues when compared with rJerR21. The evidence presented in this article converges on the hypothesis that dynamic differences between the α 1 β 1 recognition loops of rJerR21 and rJerK21 may influence the thermodynamics of their receptor recognition and binding. A decrease in the μs‐ms time scale may impair the binding affinity by reducing the rate of possible conformations that the rJerK21 can adopt in this time scale. Proteins 2011; © 2011 Wiley‐Liss, Inc.