1g36
From Proteopedia
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| - | [[Image:1g36.jpg|left|200px]] | + | [[Image:1g36.jpg|left|200px]] |
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| - | '''TRYPSIN INHIBITOR COMPLEX''' | + | {{Structure |
| + | |PDB= 1g36 |SIZE=350|CAPTION= <scene name='initialview01'>1g36</scene>, resolution 1.90Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=R11:4-{[1-METHYL-5-(2-METHYL-BENZOIMIDAZOL-1-YLMETHYL)-1H-BENZOIMIDAZOL-2-YLMETHYL]-AMINO}-BENZAMIDINE'>R11</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''TRYPSIN INHIBITOR COMPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1G36 is a [ | + | 1G36 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G36 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors., Nar H, Bauer M, Schmid A, Stassen JM, Wienen W, Priepke HW, Kauffmann IK, Ries UJ, Hauel NH, Structure. 2001 Jan 10;9(1):29-37. PMID:[http:// | + | Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors., Nar H, Bauer M, Schmid A, Stassen JM, Wienen W, Priepke HW, Kauffmann IK, Ries UJ, Hauel NH, Structure. 2001 Jan 10;9(1):29-37. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11342132 11342132] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: blood coagulation cascade]] | [[Category: blood coagulation cascade]] | ||
[[Category: factor xa]] | [[Category: factor xa]] | ||
| - | [[Category: inhibitor | + | [[Category: inhibitor complex]] |
[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''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 11:17:33 2008'' |
Revision as of 09:17, 20 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TRYPSIN INHIBITOR COMPLEX
Overview
BACKGROUND: A major current focus of pharmaceutical research is the development of selective inhibitors of the blood coagulation enzymes thrombin or factor Xa to be used as orally bioavailable anticoagulant drugs in thromboembolic disorders and in the prevention of venous and arterial thrombosis. Simultaneous direct inhibition of thrombin and factor Xa by synthetic proteinase inhibitors as a novel approach to antithrombotic therapy could result in potent anticoagulants with improved pharmacological properties. RESULTS: The binding mode of such dual specific inhibitors of thrombin and factor Xa was determined for the first time by comparative crystallography using human alpha-thrombin, human des-Gla (1--44) factor Xa and bovine trypsin as the ligand receptors. The benzamidine-based inhibitors utilize two different conformations for the interaction with thrombin and factor Xa/trypsin, which are evoked by the steric requirements of the topologically different S2 subsites of the enzymes. Compared to the unliganded forms of the proteinases, ligand binding induces conformational adjustments of thrombin and factor Xa active site residues indicative of a pronounced induced fit mechanism. CONCLUSION: The structural data reveal the molecular basis for a desired unselective inhibition of the two key components of the blood coagulation cascade. The 4-(1-methyl-benzimidazole-2-yl)-methylamino-benzamidine moieties of the inhibitors are able to fill both the small solvent accessible as well as the larger hydrophobic S2 pockets of factor Xa and thrombin, respectively. Distal fragments of the inhibitors are identified which fit into both the cation hole/aromatic box of factor Xa and the hydrophobic aryl binding site of thrombin. Thus, binding constants in the medium-to-low nanomolar range are obtained against both enzymes.
About this Structure
1G36 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition promiscuity of dual specific thrombin and factor Xa blood coagulation inhibitors., Nar H, Bauer M, Schmid A, Stassen JM, Wienen W, Priepke HW, Kauffmann IK, Ries UJ, Hauel NH, Structure. 2001 Jan 10;9(1):29-37. PMID:11342132
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