2ocv

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{{STRUCTURE_2ocv| PDB=2ocv | SCENE= }}
{{STRUCTURE_2ocv| PDB=2ocv | SCENE= }}
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'''Structural basis of Na+ activation mimicry in murine thrombin'''
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===Structural basis of Na+ activation mimicry in murine thrombin===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_17428793}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17428793 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17428793}}
==About this Structure==
==About this Structure==
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==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://www.ncbi.nlm.nih.gov/pubmed/17428793 17428793]
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]
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Molecular dissection of Na+ binding to thrombin., Pineda AO, Carrell CJ, Bush LA, Prasad S, Caccia S, Chen ZW, Mathews FS, Di Cera E, J Biol Chem. 2004 Jul 23;279(30):31842-53. Epub 2004 May 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15152000 15152000]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Mathews, F S.]]
[[Category: Mathews, F S.]]
[[Category: Serine protease]]
[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:37:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:06:12 2008''

Revision as of 08:06, 29 July 2008

Image:2ocv.png

Template:STRUCTURE 2ocv

Structural basis of Na+ activation mimicry in murine thrombin

Template:ABSTRACT PUBMED 17428793

About this Structure

2OCV is a Protein complex structure of sequences from Mus musculus. 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

Molecular dissection of Na+ binding to thrombin., Pineda AO, Carrell CJ, Bush LA, Prasad S, Caccia S, Chen ZW, Mathews FS, Di Cera E, J Biol Chem. 2004 Jul 23;279(30):31842-53. Epub 2004 May 19. PMID:15152000

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