1bmn: Difference between revisions
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==Overview== | ==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, ... | 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. | ||
==About this Structure== | ==About this Structure== | ||
1BMN is a | 1BMN is a [http://en.wikipedia.org/wiki/Protein_complex 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] with BM9 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Structure known Active Site: ACT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1BMN OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:44:02 2007'' | ||
