5hpg
From Proteopedia
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| - | [[Image:5hpg.gif|left|200px]] | + | [[Image:5hpg.gif|left|200px]] |
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| - | '''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN''' | + | {{Structure |
| + | |PDB= 5hpg |SIZE=350|CAPTION= <scene name='initialview01'>5hpg</scene>, resolution 1.66Å | ||
| + | |SITE= <scene name='pdbsite=LBS:LYS+Binding+Site'>LBS</scene> | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 5HPG is a [ | + | 5HPG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HPG OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/9521645 9521645] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Plasmin]] | [[Category: Plasmin]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:12:22 2008'' |
Revision as of 17:12, 20 March 2008
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| , resolution 1.66Å | |||||||
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| Sites: | |||||||
| Activity: | Plasmin, with EC number 3.4.21.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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