1uvs
From Proteopedia
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| - | [[Image:1uvs.jpg|left|200px]] | + | [[Image:1uvs.jpg|left|200px]] |
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| - | '''BOVINE THROMBIN--BM51.1011 COMPLEX''' | + | {{Structure |
| + | |PDB= 1uvs |SIZE=350|CAPTION= <scene name='initialview01'>1uvs</scene>, resolution 2.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=I11:[[CYCLOHEXANESULFONYL-GLYCYL]-3[PYRIDIN-4-YL-AMINOMETHYL]ALANYL]PIPERIDINE'>I11</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= | ||
| + | }} | ||
| + | |||
| + | '''BOVINE THROMBIN--BM51.1011 COMPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UVS is a [ | + | 1UVS 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=1UVS OCA]. |
==Reference== | ==Reference== | ||
| - | Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design., Engh RA, Brandstetter H, Sucher G, Eichinger A, Baumann U, Bode W, Huber R, Poll T, Rudolph R, von der Saal W, Structure. 1996 Nov 15;4(11):1353-62. PMID:[http:// | + | Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design., Engh RA, Brandstetter H, Sucher G, Eichinger A, Baumann U, Bode W, Huber R, Poll T, Rudolph R, von der Saal W, Structure. 1996 Nov 15;4(11):1353-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8939759 8939759] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:37:24 2008'' |
Revision as of 12:37, 20 March 2008
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| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
BOVINE THROMBIN--BM51.1011 COMPLEX
Contents |
Overview
BACKGROUND: The explosive growth in the rate of X-ray determination of protein structures is fuelled largely by the expectation that structural information will be useful for pharmacological and biotechnological applications. For example, there have been intensive efforts to develop orally administrable antithrombotic drugs using information about the crystal structures of blood coagulation factors, including thrombin. Most of the low molecular weight thrombin inhibitors studied so far are based on arginine and benzamidine. We sought to expand the database of information on thrombin-inhibitor binding by studying new classes of inhibitors. RESULTS: We report the structures of three new inhibitors complexed with thrombin, two based on 4-aminopyridine and one based on naphthamidine. We observe several geometry changes in the protein main chain and side chains which accompany inhibitor binding. The two inhibitors based on 4-aminopyridine bind in notably different ways: one forms a water-mediated hydrogen bond to the active site Ser195, the other induces a rotation of the Ser214-Trp215 peptide plane that is unprecedented in thrombin structures. These binding modes also differ in their 'weak' interactions, including CH-O hydrogen bonds and interactions between water molecules and aromatic pi-clouds. Induced-fit structural changes were also seen in the structure of the naphthamidine inhibitor complex. CONCLUSIONS: Protein flexibility and variable water structures are essential elements in protein-ligand interactions. Ligand design strategies that fail to take this into account may overlook or underestimate the potential of lead structures. Further, the significance of 'weak' interactions must be considered both in crystallographic refinement and in analysis of binding mechanisms.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1UVS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design., Engh RA, Brandstetter H, Sucher G, Eichinger A, Baumann U, Bode W, Huber R, Poll T, Rudolph R, von der Saal W, Structure. 1996 Nov 15;4(11):1353-62. PMID:8939759
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