1bmn: Difference between revisions
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[[Image:1bmn.gif|left|200px]]<br /> | [[Image:1bmn.gif|left|200px]]<br /><applet load="1bmn" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1bmn" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1bmn, resolution 2.8Å" /> | caption="1bmn, resolution 2.8Å" /> | ||
'''HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)'''<br /> | '''HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
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] | 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] Known structural/functional Site: <scene name='pdbsite=ACT:Active Site'>ACT</scene>. 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]] | ||
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Revision as of 15:20, 18 December 2007
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HUMAN ALPHA-THROMBIN COMPLEXED WITH [S-(R*,R*)]-1-(AMINOIMINOMETHYL)-N-[[1-[N-[(2-NAPHTHALENYLSULFONYL)-L-SERYL]-PYRROLIDINYL]METHYL]-3-PIPERIDENECARBOXAMIDE (BMS-189090)
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1BMN is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with BM9 as ligand. Active as Thrombin, with EC number 3.4.21.5 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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