1tpk
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of the kringle 2 domain of tissue plasminogen | + | The crystal structure of the kringle 2 domain of tissue plasminogen activator was determined and refined at a resolution of 2.43 A. The overall fold of the molecule is similar to that of prothrombin kringle 1 and plasminogen kringle 4; however, there are differences in the lysine binding pocket, and two looping regions, which include insertions in kringle 2, take on very different conformations. Based on a comparison of the overall structural homology between kringle 2 and kringle 4, a new sequence alignment for kringle domains is proposed that results in a division of kringle domains into two groups, consistent with their proposed evolutionary relation. The crystal structure shows a strong interaction between a lysine residue of one molecule and the lysine/fibrin binding pocket of a noncrystallographically related neighbor. This interaction represents a good model of a bound protein ligand and is the first such ligand that has been observed in a kringle binding pocket. The structure shows an intricate network of interactions both among the binding pocket residues and between binding pocket residues and the lysine ligand. A lysine side chain is identified as the positively charged group positioned to interact with the carboxylate of lysine and lysine analogue ligands. In addition, a chloride ion is located in the kringle-kringle interface and contributes to the observed interaction between kringle molecules. |
==Disease== | ==Disease== | ||
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[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Devos, A | + | [[Category: Devos, A M.]] |
| - | [[Category: Kelley, R | + | [[Category: Kelley, R F.]] |
| - | [[Category: Kossiakoff, A | + | [[Category: Kossiakoff, A A.]] |
[[Category: Padmanabhan, K.]] | [[Category: Padmanabhan, K.]] | ||
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
| - | [[Category: Ultsch, M | + | [[Category: Ultsch, M H.]] |
| - | [[Category: Westbrook, M | + | [[Category: Westbrook, M L.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: plasminogen activator]] | [[Category: plasminogen activator]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:16:07 2008'' |
Revision as of 13:16, 21 February 2008
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CRYSTAL STRUCTURE OF THE KRINGLE-2 DOMAIN OF TISSUE PLASMINOGEN ACTIVATOR AT 2.4-ANGSTROMS RESOLUTION
Contents |
Overview
The crystal structure of the kringle 2 domain of tissue plasminogen activator was determined and refined at a resolution of 2.43 A. The overall fold of the molecule is similar to that of prothrombin kringle 1 and plasminogen kringle 4; however, there are differences in the lysine binding pocket, and two looping regions, which include insertions in kringle 2, take on very different conformations. Based on a comparison of the overall structural homology between kringle 2 and kringle 4, a new sequence alignment for kringle domains is proposed that results in a division of kringle domains into two groups, consistent with their proposed evolutionary relation. The crystal structure shows a strong interaction between a lysine residue of one molecule and the lysine/fibrin binding pocket of a noncrystallographically related neighbor. This interaction represents a good model of a bound protein ligand and is the first such ligand that has been observed in a kringle binding pocket. The structure shows an intricate network of interactions both among the binding pocket residues and between binding pocket residues and the lysine ligand. A lysine side chain is identified as the positively charged group positioned to interact with the carboxylate of lysine and lysine analogue ligands. In addition, a chloride ion is located in the kringle-kringle interface and contributes to the observed interaction between kringle molecules.
Disease
Known disease associated with this structure: Plasminogen activator deficiency OMIM:[173370]
About this Structure
1TPK is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Hydrolase, with EC number and 3.4.21.73 3.4.21.68 and 3.4.21.73 Full crystallographic information is available from OCA.
Reference
Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution., de Vos AM, Ultsch MH, Kelley RF, Padmanabhan K, Tulinsky A, Westbrook ML, Kossiakoff AA, Biochemistry. 1992 Jan 14;31(1):270-9. PMID:1310033
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