5hpg: Difference between revisions

==Overview==

The X-ray crystal structure of the recombinant (r) kringle 5 domain of, human plasminogen (K5HPg) has been solved by molecular replacement methods, using K1HPg as a model and refined at 1.7 A resolution to an R factor of, 16.6%. The asymmetric unit of K5HPg is composed of two molecules related, by a noncrystallographic 2-fold rotation axis approximately parallel to, the z-direction. The lysine binding site (LBS) is defined by the regions, His33-Thr37, Pro54-Val58, Pro61-Tyr64, and Leu71-Tyr74 and is occupied in, the apo-form by water molecules. A unique feature of the LBS of apo-K5HPg, is the substitution by Leu71 for the basic amino acid, arginine, that in, other kringle polypeptides forms the donor cationic center for the, carboxylate group of omega-amino acid ligands. While wild-type (wt), r-K5HPg interacted weakly with these types of ligands, replacement by, site-directed mutagenesis of Leu71 by arginine led to substantially, increased affinity of the ligands for the LBS of K5HPg. As a result, binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was, restored to levels displayed by the companion much stronger affinity HPg, kringles, K1HPg and K4HPg. Correspondingly, alkylamine binding to, r-K5HPg[L71R] was considerably attenuated from that shown by wtr-K5HPg., Thus, employing a rational design strategy based on the crystal structure, of K5HPg, successful remodeling of the LBS has been accomplished, and has, resulted in the conversion of a weak ligand binding kringle to one that, possesses an affinity for omega-amino acids that is similar to K1HPg and, K4HPg.

==About this Structure==

[[Category: serine protease]]