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5hpg
From Proteopedia
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| - | [[Image:5hpg.gif|left|200px]]<br /> | + | [[Image:5hpg.gif|left|200px]]<br /><applet load="5hpg" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="5hpg" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="5hpg, resolution 1.66Å" /> | caption="5hpg, resolution 1.66Å" /> | ||
'''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN'''<br /> | '''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 5HPG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] | + | 5HPG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] Known structural/functional Site: <scene name='pdbsite=LBS:LYS Binding Site'>LBS</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=5HPG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 20:46:39 2007'' |
Revision as of 18:36, 18 December 2007
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STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN
Contents |
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.
Disease
Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this Structure
5HPG is a Single protein structure of sequence from Homo sapiens. Active as Plasmin, with EC number 3.4.21.7 Known structural/functional Site: . 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
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