1dwb
From Proteopedia
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| - | [[Image:1dwb.gif|left|200px]] | + | [[Image:1dwb.gif|left|200px]] |
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| - | '''CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS''' | + | {{Structure |
| + | |PDB= 1dwb |SIZE=350|CAPTION= <scene name='initialview01'>1dwb</scene>, resolution 3.16Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</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= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DWB is a [ | + | 1DWB is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] 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=1DWB OCA]. |
==Reference== | ==Reference== | ||
| - | Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors., Banner DW, Hadvary P, J Biol Chem. 1991 Oct 25;266(30):20085-93. PMID:[http:// | + | Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors., Banner DW, Hadvary P, J Biol Chem. 1991 Oct 25;266(30):20085-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1939071 1939071] |
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: hydrolase(serine proteinase)]] | [[Category: hydrolase(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 10:45:31 2008'' |
Revision as of 08:45, 20 March 2008
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| , resolution 3.16Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS
Contents |
Overview
The mode of binding of four active-site directed inhibitors to human thrombin has been determined by x-ray crystallographic analysis. The inhibitors studied are benzamidine, PPACK, NAPAP, and MD-805, of which the last three are compounds evolved specifically to inhibit thrombin. Crystal structures were determined in the presence of both the inhibitor and the undecapeptide [des-amino Asp55]hirudin(55-65) which binds distant from the active site. Despite having significantly different chemical structures, NAPAP and MD-805 bind to thrombin in a very similar "inhibitor binding mode" which is not that expected by direct analogy with the binding of substrate. Both inhibitors bind to thrombin in a similar way as to trypsin, but thrombin has an extra loop, the "Tyr-Pro-Pro-Trp loop," not present in trypsin, which gives further binding interactions and is seen to move somewhat to accommodate binding of the different inhibitors. The fact that NAPAP and MD-805 require different stereochemistry for potent inhibition is demonstrated, and its structural basis clarified. The wealth of data on analogs and variants of these lead compounds is shown to be compatible with this inhibitor binding mode.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1DWB is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors., Banner DW, Hadvary P, J Biol Chem. 1991 Oct 25;266(30):20085-93. PMID:1939071
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