1mh0
From Proteopedia
(New page: 200px<br /> <applet load="1mh0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mh0, resolution 2.80Å" /> '''Crystal structure o...) |
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| - | [[Image:1mh0.gif|left|200px]]<br /> | + | [[Image:1mh0.gif|left|200px]]<br /><applet load="1mh0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mh0" size=" | + | |
caption="1mh0, resolution 2.80Å" /> | caption="1mh0, resolution 2.80Å" /> | ||
'''Crystal structure of the anticoagulant slow form of thrombin'''<br /> | '''Crystal structure of the anticoagulant slow form of thrombin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Using the thrombin mutant R77aA devoid of the site of autoproteolytic | + | Using the thrombin mutant R77aA devoid of the site of autoproteolytic degradation at exosite I, we have solved for the first time the structure of thrombin free of any inhibitors and effector molecules and stabilized in the Na(+)-free slow form. The slow form shows subtle differences compared with the currently available structures of the Na(+)-bound fast form that carry inhibitors at the active site or exosite I. The most notable differences are the displacement of Asp-189 in the S1 specificity pocket, a downward shift of the 190-193 strand, a rearrangement of the side chain of Glu-192, and a significant shift in the position of the catalytic Ser-195 that is no longer within H-bonding distance from His-57. The structure of the slow form explains the reduced specificity toward synthetic and natural substrates and suggests a molecular basis for its anticoagulant properties. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1MH0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 1MH0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MH0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Cera, E | + | [[Category: Cera, E Di.]] |
| - | [[Category: Pineda, A | + | [[Category: Pineda, A O.]] |
[[Category: Savvides, S.]] | [[Category: Savvides, S.]] | ||
[[Category: Waksman, G.]] | [[Category: Waksman, G.]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:05 2008'' |
Revision as of 11:55, 21 February 2008
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Crystal structure of the anticoagulant slow form of thrombin
Contents |
Overview
Using the thrombin mutant R77aA devoid of the site of autoproteolytic degradation at exosite I, we have solved for the first time the structure of thrombin free of any inhibitors and effector molecules and stabilized in the Na(+)-free slow form. The slow form shows subtle differences compared with the currently available structures of the Na(+)-bound fast form that carry inhibitors at the active site or exosite I. The most notable differences are the displacement of Asp-189 in the S1 specificity pocket, a downward shift of the 190-193 strand, a rearrangement of the side chain of Glu-192, and a significant shift in the position of the catalytic Ser-195 that is no longer within H-bonding distance from His-57. The structure of the slow form explains the reduced specificity toward synthetic and natural substrates and suggests a molecular basis for its anticoagulant properties.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1MH0 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Crystal structure of the anticoagulant slow form of thrombin., Pineda AO, Savvides SN, Waksman G, Di Cera E, J Biol Chem. 2002 Oct 25;277(43):40177-80. Epub 2002 Aug 29. PMID:12205081
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