1qbv: Difference between revisions
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'''CRYSTAL STRUCTURE OF THROMBIN COMPLEXED WITH AN GUANIDINE-MIMETIC INHIBITOR''' | {{Structure | ||
|PDB= 1qbv |SIZE=350|CAPTION= <scene name='initialview01'>1qbv</scene>, resolution 1.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PPX:[PHENYLALANINYL-PROLINYL]-[2-(PYRIDIN-4-YLAMINO)-ETHYL]-AMINE'>PPX</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= | |||
}} | |||
'''CRYSTAL STRUCTURE OF THROMBIN COMPLEXED WITH AN GUANIDINE-MIMETIC INHIBITOR''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1QBV is a [ | 1QBV is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Hirudinaria_manillensis Hirudinaria manillensis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QBV OCA]. | ||
==Reference== | ==Reference== | ||
Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes., Bone R, Lu T, Illig CR, Soll RM, Spurlino JC, J Med Chem. 1998 Jun 4;41(12):2068-75. PMID:[http:// | Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes., Bone R, Lu T, Illig CR, Soll RM, Spurlino JC, J Med Chem. 1998 Jun 4;41(12):2068-75. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9622548 9622548] | ||
[[Category: Hirudinaria manillensis]] | [[Category: Hirudinaria manillensis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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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 13:35:36 2008'' | ||
Revision as of 11:35, 20 March 2008
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| 1qbv, resolution 1.80Å | |||||||||||||
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| Ligands: | PPX | ||||||||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
CRYSTAL STRUCTURE OF THROMBIN COMPLEXED WITH AN GUANIDINE-MIMETIC INHIBITOR
Overview
The structure of the noncovalent complex of human alpha-thrombin with a nonpeptide inhibitor containing a central phenyl scaffold, N-[2-[5-methyl-3-(2-chlorophenylsulfonyloxy)phenoxy]ethyl]-N- methyl-4 -aminopyridine (1), has been determined to 2.20 A resolution. In addition, the thrombin-bound structures of two distinct amino acid-based inhibitors (3 and 4) containing different aminopyridine-derived guanidine mimetics have been determined. Each compound occupies the same region of the active site and projects an aminopyridine, a central hydrophobic group, and an aryl group, into the S1, S2, and aryl subsites on thrombin. Nonpeptide 1 forms only one direct intermolecular hydrogen bond to the thrombin active site and forms no hydrogen bonds to ordered molecules of solvent. Close contacts are observed between main-chain carbonyl groups on thrombin and the edges of the central phenyl and aminopyridine rings and the sulfonyl group of 1 such that atoms carrying opposite partial charges are juxtaposed. Aminopyridine groups in 3 and 4 also form close contacts with the edges of carbonyl groups on thrombin and are flexibly accommodated in the S1 subsite. Superposition of the bound conformations of 1 and D-Phe-Pro-amidobutylguanidine (2) revealed that the central phenyl scaffold of 1 substitutes for the peptide main chain of 2.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1QBV is a Protein complex structure of sequences from Hirudinaria manillensis and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes., Bone R, Lu T, Illig CR, Soll RM, Spurlino JC, J Med Chem. 1998 Jun 4;41(12):2068-75. PMID:9622548
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