1tq7

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[[Image:1tq7.jpg|left|200px]]<br /><applet load="1tq7" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1tq7.jpg|left|200px]]
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caption="1tq7, resolution 2.40&Aring;" />
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'''Crystal structure of the anticoagulant thrombin mutant W215A/E217A bound to PPACK'''<br />
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{{Structure
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|PDB= 1tq7 |SIZE=350|CAPTION= <scene name='initialview01'>1tq7</scene>, resolution 2.40&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=CH2:METHYLENE GROUP'>CH2</scene>
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|ACTIVITY= [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]
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|GENE= F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal structure of the anticoagulant thrombin mutant W215A/E217A bound to PPACK'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1TQ7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CH2:'>CH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1TQ7 OCA].
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1TQ7 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=1TQ7 OCA].
==Reference==
==Reference==
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The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket., Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E, J Biol Chem. 2004 Sep 17;279(38):39824-8. Epub 2004 Jul 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15252033 15252033]
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The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket., Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E, J Biol Chem. 2004 Sep 17;279(38):39824-8. Epub 2004 Jul 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15252033 15252033]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: thrombin]]
[[Category: thrombin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:16:12 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:21:43 2008''

Revision as of 12:21, 20 March 2008

Image:1tq7.jpg


PDB ID 1tq7

Drag the structure with the mouse to rotate
, resolution 2.40Å
Ligands: , and
Gene: F2 (Homo sapiens)
Activity: Thrombin, with EC number 3.4.21.5
Coordinates: save as pdb, mmCIF, xml



Crystal structure of the anticoagulant thrombin mutant W215A/E217A bound to PPACK


Contents

Overview

The thrombin mutant W215A/E217A features a drastically impaired catalytic activity toward chromogenic and natural substrates but efficiently activates the anticoagulant protein C in the presence of thrombomodulin. As the remarkable anticoagulant properties of this mutant continue to be unraveled in preclinical studies, we solved the x-ray crystal structures of its free form and its complex with the active site inhibitor H-d-Phe-Pro-Arg-CH(2)Cl (PPACK). The PPACK-bound structure of W215A/E217A is identical to the structure of the PPACK-bound slow form of thrombin. On the other hand, the structure of the free form reveals a collapse of the 215-217 strand that crushes the primary specificity pocket. The collapse results from abrogation of the stacking interaction between Phe-227 and Trp-215 and the polar interactions of Glu-217 with Thr-172 and Lys-224. Other notable changes are a rotation of the carboxylate group of Asp-189, breakage of the H-bond between the catalytic residues Ser-195 and His-57, breakage of the ion pair between Asp-222 and Arg-187, and significant disorder in the 186- and 220-loops that define the Na(+) site. These findings explain the impaired catalytic activity of W215A/E217A and demonstrate that the analysis of the molecular basis of substrate recognition by thrombin and other proteases requires crystallization of both the free and bound forms of the enzyme.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1TQ7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket., Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E, J Biol Chem. 2004 Sep 17;279(38):39824-8. Epub 2004 Jul 13. PMID:15252033

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