1bmn
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1bmn.gif|left|200px]] | + | [[Image:1bmn.gif|left|200px]] |
| - | + | ||
| - | '''HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)''' | + | {{Structure |
| + | |PDB= 1bmn |SIZE=350|CAPTION= <scene name='initialview01'>1bmn</scene>, resolution 2.8Å | ||
| + | |SITE= <scene name='pdbsite=ACT:Active+Site'>ACT</scene> | ||
| + | |LIGAND= <scene name='pdbligand=BM9:[S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-3-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE'>BM9</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= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1BMN is a [ | + | 1BMN 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=1BMN OCA]. |
==Reference== | ==Reference== | ||
| - | Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090., Malley MF, Tabernero L, Chang CY, Ohringer SL, Roberts DG, Das J, Sack JS, Protein Sci. 1996 Feb;5(2):221-8. PMID:[http:// | + | Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090., Malley MF, Tabernero L, Chang CY, Ohringer SL, Roberts DG, Das J, Sack JS, Protein Sci. 1996 Feb;5(2):221-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8745399 8745399] |
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 24: | Line 33: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''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 10:13:00 2008'' |
Revision as of 08:13, 20 March 2008
| |||||||
| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)
Contents |
Overview
The crystallographic structures of the ternary complexes of human alpha-thrombin with hirugen (a sulfated hirudin fragment) and the small-molecule active site thrombin inhibitors BMS-186282 and BMS-189090 have been determined at 2.6 and 2.8 A. In both cases, the inhibitors, which adopt very similar bound conformations, bind in an antiparallel beta-strand arrangement relative to the thrombin main chain in a manner like that reported for PPACK, D-Phe-Pro-Arg-CH2Cl. They do, however, exhibit differences in the binding of the alkyl guanidine moiety in the specificity pocket. Numerous hydrophilic and hydrophobic interactions serve to stabilize the inhibitors in the binding pocket. Although PPACK forms covalent bonds to both serine and the histidine of the catalytic triad of thrombin, neither BMS-186282 nor BMS-189090 bind covalently and only BMS-186282 forms a hydrogen bond to the serine of the catalytic triad. Both inhibitors bind with high affinity (Ki = 79 nM and 3.6 nM, respectively) and are highly selective for thrombin over trypsin and other serine proteases.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1BMN is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystallographic determination of the structures of human alpha-thrombin complexed with BMS-186282 and BMS-189090., Malley MF, Tabernero L, Chang CY, Ohringer SL, Roberts DG, Das J, Sack JS, Protein Sci. 1996 Feb;5(2):221-8. PMID:8745399
Page seeded by OCA on Thu Mar 20 10:13:00 2008
