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3bv9
From Proteopedia
(New page: 200px<br /><applet load="3bv9" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bv9, resolution 1.80Å" /> '''Structure of Thrombi...) |
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| - | [[Image:3bv9.jpg|left|200px]] | + | [[Image:3bv9.jpg|left|200px]] |
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| - | '''Structure of Thrombin Bound to the Inhibitor FM19''' | + | {{Structure |
| + | |PDB= 3bv9 |SIZE=350|CAPTION= <scene name='initialview01'>3bv9</scene>, resolution 1.80Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Oic+Binding+Site+For+Residue+C+402'>AC1</scene>, <scene name='pdbsite=AC2:4ph+Binding+Site+For+Residue+C+405'>AC2</scene>, <scene name='pdbsite=AC3:Iod+Binding+Site+For+Residue+B+303'>AC3</scene>, <scene name='pdbsite=AC4:Na+Binding+Site+For+Residue+B+307'>AC4</scene>, <scene name='pdbsite=AC5:Nh2+Binding+Site+For+Residue+C+406'>AC5</scene> and <scene name='pdbsite=AC6:Gol+Binding+Site+For+Residue+B+305'>AC6</scene> | ||
| + | |LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |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] | ||
| + | |GENE= F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of Thrombin Bound to the Inhibitor FM19''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 3BV9 is a [ | + | 3BV9 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=3BV9 OCA]. |
==Reference== | ==Reference== | ||
| - | 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:// | + | 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: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 45: | Line 54: | ||
[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:01:28 2008'' |
Revision as of 17:01, 20 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , and | ||||||
| Ligands: | , , and | ||||||
| Gene: | F2 (Homo sapiens) | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Thrombin Bound to the Inhibitor FM19
Overview
Na(+) binding near the primary specificity pocket of thrombin promotes the procoagulant, prothrombotic, and signaling functions of the enzyme. The effect is mediated allosterically by a communication between the Na(+) site and regions involved in substrate recognition. Using a panel of 78 Ala mutants of thrombin, we have mapped the allosteric core of residues that are energetically linked to Na(+) binding. These residues are Asp-189, Glu-217, Asp-222, and Tyr-225, all in close proximity to the bound Na(+). Among these residues, Asp-189 shares with Asp-221 the important function of transducing Na(+) binding into enhanced catalytic activity. None of the residues of exosite I, exosite II, or the 60-loop plays a significant role in Na(+) binding and allosteric transduction. X-ray crystal structures of the Na(+)-free (slow) and Na(+)-bound (fast) forms of thrombin, free or bound to the active site inhibitor H-d-Phe-Pro-Arg-chloromethyl-ketone, document the conformational changes induced by Na(+) binding. The slow --> fast transition results in formation of the Arg-187:Asp-222 ion pair, optimal orientation of Asp-189 and Ser-195 for substrate binding, and a significant shift of the side chain of Glu-192 linked to a rearrangement of the network of water molecules that connect the bound Na(+) to Ser-195 in the active site. The changes in the water network and the allosteric core explain the thermodynamic signatures linked to Na(+) binding and the mechanism of thrombin activation by Na(+). The role of the water network uncovered in this study establishes a new paradigm for the allosteric regulation of thrombin and other Na(+)-activated enzymes involved in blood coagulation and the immune response.
About this Structure
3BV9 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 19:01:28 2008
Categories: Homo sapiens | Protein complex | Thrombin | Burke, F. | Cera, E Di. | Chen, A. | Chen, Z. | Hilfinger, J. | Lucchesi, B R. | Mosberg, H I. | Nieman, M T. | Ricketts, D. | Schmaier, A H. | Sweigert, J. | Warnock, M. | Zhou, Y. | GOL | IOD | NA | NH2 | Acute phase | Blood coagulation | Calcium | Cleavage on pair of basic residue | Disease mutation | Gamma-carboxyglutamic acid | Glycoprotein | Hydrolase | Kringle | Polymorphism | Secreted | Serine protease | Zymogen
