|
|
| Line 1: |
Line 1: |
| [[Image:2od3.gif|left|200px]] | | {{Seed}} |
| | [[Image:2od3.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2od3| PDB=2od3 | SCENE= }} | | {{STRUCTURE_2od3| PDB=2od3 | SCENE= }} |
|
| |
|
| '''Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.'''
| | ===Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| Unlike human thrombin, murine thrombin lacks Na+ activation due to the charge reversal substitution D222K in the Na+ binding loop. However, the enzyme is functionally stabilized in a Na+-bound form and is highly active toward physiologic substrates. The structural basis of this peculiar property is unknown. Here, we present the 2.2 A resolution x-ray crystal structure of murine thrombin in the absence of inhibitors and salts. The enzyme assumes an active conformation, with Ser-195, Glu-192, and Asp-189 oriented as in the Na+-bound fast form of human thrombin. Lys-222 completely occludes the pore of entry to the Na+ binding site and positions its side chain inside the pore, with the Nzeta atom H-bonded to the backbone oxygen atoms of Lys-185, Asp-186b, and Lys-186d. The same architecture is observed in the 1.75 A resolution structure of a thrombin chimera in which the human enzyme carries all residues defining the Na+ pore in the murine enzyme. These findings demonstrate that Na+ activation in thrombin is linked to the architecture of the Na+ pore. The molecular strategy of Na+ activation mimicry unraveled for murine thrombin is relevant to serine proteases and enzymes activated by monovalent cations in general.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17428793}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17428793 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_17428793}} |
|
| |
|
| ==Disease== | | ==Disease== |
| Line 32: |
Line 36: |
| [[Category: Mathews, F S.]] | | [[Category: Mathews, F S.]] |
| [[Category: Serine protease]] | | [[Category: Serine protease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:38:53 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:14:18 2008'' |
