2od3
From Proteopedia
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Human thrombin chimera with human residues 184a, 186, 186a, 186b, 186c and 222 replaced by murine thrombin equivalents.
Contents |
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.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
2OD3 is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Full crystallographic information is available from OCA.
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:17428793
Page seeded by OCA on Mon Nov 12 23:09:30 2007
