2od3: Difference between revisions
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[[Image:2od3.gif|left|200px]] | [[Image:2od3.gif|left|200px]] | ||
'''Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.''' | {{Structure | ||
|PDB= 2od3 |SIZE=350|CAPTION= <scene name='initialview01'>2od3</scene>, resolution 1.75Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | |||
|ACTIVITY= | |||
|GENE= F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2OD3 is a [ | 2OD3 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=2OD3 OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis of Na+ activation mimicry in murine thrombin., Marino F, Chen ZW, Ergenekan CE, Bush-Pelc LA, Mathews FS, Di Cera E, J Biol Chem. 2007 Jun 1;282(22):16355-61. Epub 2007 Apr 10. PMID:[http:// | Structural basis of Na+ activation mimicry in murine thrombin., Marino F, Chen ZW, Ergenekan CE, Bush-Pelc LA, Mathews FS, Di Cera E, J Biol Chem. 2007 Jun 1;282(22):16355-61. Epub 2007 Apr 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17428793 17428793] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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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 17:58:06 2008'' | ||
Revision as of 18:58, 20 March 2008
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| , resolution 1.75Å | |||||||
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| Ligands: | |||||||
| Gene: | F2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
2OD3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of Na+ activation mimicry in murine thrombin., Marino F, Chen ZW, Ergenekan CE, Bush-Pelc LA, Mathews FS, Di Cera E, J Biol Chem. 2007 Jun 1;282(22):16355-61. Epub 2007 Apr 10. PMID:17428793
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