5hpg
From Proteopedia
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'''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN''' | '''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN''' | ||
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[[Category: Mochalkin, I.]] | [[Category: Mochalkin, I.]] | ||
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
| - | [[Category: | + | [[Category: Fibrinolysis]] |
| - | [[Category: | + | [[Category: Human plasminogen]] |
| - | [[Category: | + | [[Category: Kringle 5]] |
| - | [[Category: | + | [[Category: Serine protease]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:35:13 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:35, 4 May 2008
STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN
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
5HPG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen., Chang Y, Mochalkin I, McCance SG, Cheng B, Tulinsky A, Castellino FJ, Biochemistry. 1998 Mar 10;37(10):3258-71. PMID:9521645 Page seeded by OCA on Sun May 4 22:35:13 2008
