2ocv: Difference between revisions

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==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.

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.

==About this Structure==

Line 10:

==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://ispc.weizmann.ac.il//pmbin/getpm?pmid=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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17428793 17428793]

[[Category: Mus musculus]]

[[Category: Protein complex]]

[[Category: Bush, L.A.]]

[[Category: Bush, L A.]]

[[Category: Cera, E.Di.]]

[[Category: Cera, E Di.]]

[[Category: Chen, Z.]]

[[Category: Ergenekan, C.E.]]

[[Category: Ergenekan, C E.]]

[[Category: Marino, F.]]

[[Category: Mathews, F.S.]]

[[Category: Mathews, F S.]]

[[Category: NAG]]

[[Category: serine protease]]

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@@ Line 4: / Line 4: @@
 ==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.
+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.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==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://ispc.weizmann.ac.il//pmbin/getpm?pmid=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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17428793 17428793]
 [[Category: Mus musculus]]
 [[Category: Protein complex]]
-[[Category: Bush, L.A.]]
+[[Category: Bush, L A.]]
-[[Category: Cera, E.Di.]]
+[[Category: Cera, E Di.]]
 [[Category: Chen, Z.]]
-[[Category: Ergenekan, C.E.]]
+[[Category: Ergenekan, C E.]]
 [[Category: Marino, F.]]
-[[Category: Mathews, F.S.]]
+[[Category: Mathews, F S.]]
 [[Category: NAG]]
 [[Category: serine protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:53:22 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:16:59 2008''