1i5k
From Proteopedia
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| - | [[Image:1i5k.gif|left|200px]] | + | [[Image:1i5k.gif|left|200px]] |
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| - | '''STRUCTURE AND BINDING DETERMINANTS OF THE RECOMBINANT KRINGLE-2 DOMAIN OF HUMAN PLASMINOGEN TO AN INTERNAL PEPTIDE FROM A GROUP A STREPTOCOCCAL SURFACE PROTEIN''' | + | {{Structure |
| + | |PDB= 1i5k |SIZE=350|CAPTION= <scene name='initialview01'>1i5k</scene>, resolution 2.7Å | ||
| + | |SITE= | ||
| + | |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 BINDING DETERMINANTS OF THE RECOMBINANT KRINGLE-2 DOMAIN OF HUMAN PLASMINOGEN TO AN INTERNAL PEPTIDE FROM A GROUP A STREPTOCOCCAL SURFACE PROTEIN''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1I5K is a [ | + | 1I5K is a [[Protein complex]] structure of sequences 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=1I5K OCA]. |
==Reference== | ==Reference== | ||
| - | Structure and binding determinants of the recombinant kringle-2 domain of human plasminogen to an internal peptide from a group A Streptococcal surface protein., Rios-Steiner JL, Schenone M, Mochalkin I, Tulinsky A, Castellino FJ, J Mol Biol. 2001 May 11;308(4):705-19. PMID:[http:// | + | Structure and binding determinants of the recombinant kringle-2 domain of human plasminogen to an internal peptide from a group A Streptococcal surface protein., Rios-Steiner JL, Schenone M, Mochalkin I, Tulinsky A, Castellino FJ, J Mol Biol. 2001 May 11;308(4):705-19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11350170 11350170] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Plasmin]] | [[Category: Plasmin]] | ||
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[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
[[Category: human plasminogen kringle-2]] | [[Category: human plasminogen kringle-2]] | ||
| - | [[Category: | + | [[Category: kringle]] |
[[Category: vek-30]] | [[Category: vek-30]] | ||
| - | ''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 11:45:50 2008'' |
Revision as of 09:45, 20 March 2008
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| , resolution 2.7Å | |||||||
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| Activity: | Plasmin, with EC number 3.4.21.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE AND BINDING DETERMINANTS OF THE RECOMBINANT KRINGLE-2 DOMAIN OF HUMAN PLASMINOGEN TO AN INTERNAL PEPTIDE FROM A GROUP A STREPTOCOCCAL SURFACE PROTEIN
Contents |
Overview
The X-ray crystal structure of a complex of a modified recombinant kringle-2 domain of human plasminogen, K2Pg[C4G/E56D/L72Y] (mK2Pg), containing an upregulated lysine-binding site, bound to a functional 30 residue internal peptide (VEK-30) from an M-type protein of a group A Streptococcus surface protein, has been determined by molecular replacement methods using K4Pg as a model, and refined at 2.7 A resolution to a R-factor of 19.5 %. The X-ray crystal structure shows that VEK-30 exists as a nearly end-to-end alpha-helix in the complex with mK2Pg. The final structure also revealed that Arg17 and His18 of VEK-30 served as cationic loci for Asp54 and Asp56 of the consensus lysine-binding site of mK2Pg, while Glu20 of VEK-30 coordinates with Arg69 of the cationic binding site of mK2Pg. The hydrophobic ligand-binding pocket in mK2Pg, consisting primarily of Trp60 and Trp70, situated between the positive and negative centers of the lysine-binding site, is utilized in a novel manner in stabilizing the interaction with VEK-30 by forming a cation-pi-electron-mediated association with the positive side-chain of Arg17 of this peptide. Additional lysine-binding sites, as well as exosite electrostatic and hydrogen bonding interactions involving Glu9 and Lys14 of VEK-30, were observed in the structural model. The importance of these interactions were tested in solution by investigating the binding constants of synthetic variants of VEK-30 to mK2Pg, and it was found that, Lys14, Arg17, His18, and Glu20 of VEK-30 were the most critical amino acid binding determinants. With regard to the solution studies, circular dichroism analysis of the titration of VEK-30 with mK2Pg demonstrated that the peptidic alpha-helical structure increased substantially when bound to the kringle module, in agreement with the X-ray results.This investigation is the first to delineate structurally the mode of interaction of the lysine-binding site of a kringle with an internal pseudo-lysine residue of a peptide or protein that functionally interacts with a kringle module, and serves as a paradigm for this important class of interactions.
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
1I5K is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and binding determinants of the recombinant kringle-2 domain of human plasminogen to an internal peptide from a group A Streptococcal surface protein., Rios-Steiner JL, Schenone M, Mochalkin I, Tulinsky A, Castellino FJ, J Mol Biol. 2001 May 11;308(4):705-19. PMID:11350170
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