1auj

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[[Image:1auj.gif|left|200px]]<br /><applet load="1auj" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1auj, resolution 2.1&Aring;" />
 
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'''BOVINE TRYPSIN COMPLEXED TO META-CYANO-BENZYLIC INHIBITOR'''<br />
 
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==Overview==
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==BOVINE TRYPSIN COMPLEXED TO META-CYANO-BENZYLIC INHIBITOR==
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<StructureSection load='1auj' size='340' side='right'caption='[[1auj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1auj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AUJ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PPB:1-{[1-(2-AMINO-3-PHENYL-PROPIONYL)-PYRROLIDINE-2-CARBONYL]-AMINO}-2-(3-CYANO-PHENYL)-ETHANEBORONIC+ACID'>PPB</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1auj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1auj OCA], [https://pdbe.org/1auj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1auj RCSB], [https://www.ebi.ac.uk/pdbsum/1auj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1auj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/au/1auj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1auj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Highly effective thrombin inhibitors have been obtained by preparing boronic acid analogues of m-cyano-substituted phenylalanine and its incorporation into peptides. The cyano group enhances binding by several orders of magnitude. For example, Ac-(D)Phe-Pro-boroPheOH binds to thrombin with a Ki of 320 nM and the Ki of Ac-(D)Phe-Pro-boroPhe(m-CN)-OH is 0.79 nM. Protein crystal structure determination of trypsin complexed to H-(D)Phe-Pro-boroPhe(m-CN)-OH indicates that the aromatic side chain is bound in the P1 binding site and that the cyano group can act as a H-bond acceptor for the amide proton of Gly219. Enhanced binding for inhibitors containing the m-cyano group was observed for coagulation factor Xa and for the factor VIIa.tissue factor complex [Ki values of Ac-(D)Phe-Pro-boroPhe(mCN)-OH are 760 and 3.3 nM, respectively]. This result is consistent with the sequence homology of these two enzymes in the P1 binding site. Two enzymes lacking the strict homology in the P1 binding site, pancreatic kallikrein and chymotrypsin, did not exhibit significantly enhanced binding.
Highly effective thrombin inhibitors have been obtained by preparing boronic acid analogues of m-cyano-substituted phenylalanine and its incorporation into peptides. The cyano group enhances binding by several orders of magnitude. For example, Ac-(D)Phe-Pro-boroPheOH binds to thrombin with a Ki of 320 nM and the Ki of Ac-(D)Phe-Pro-boroPhe(m-CN)-OH is 0.79 nM. Protein crystal structure determination of trypsin complexed to H-(D)Phe-Pro-boroPhe(m-CN)-OH indicates that the aromatic side chain is bound in the P1 binding site and that the cyano group can act as a H-bond acceptor for the amide proton of Gly219. Enhanced binding for inhibitors containing the m-cyano group was observed for coagulation factor Xa and for the factor VIIa.tissue factor complex [Ki values of Ac-(D)Phe-Pro-boroPhe(mCN)-OH are 760 and 3.3 nM, respectively]. This result is consistent with the sequence homology of these two enzymes in the P1 binding site. Two enzymes lacking the strict homology in the P1 binding site, pancreatic kallikrein and chymotrypsin, did not exhibit significantly enhanced binding.
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==About this Structure==
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New inhibitors of thrombin and other trypsin-like proteases: hydrogen bonding of an aromatic cyano group with a backbone amide of the P1 binding site replaces binding of a basic side chain.,Lee SL, Alexander RS, Smallwood A, Trievel R, Mersinger L, Weber PC, Kettner C Biochemistry. 1997 Oct 28;36(43):13180-6. PMID:9341205<ref>PMID:9341205</ref>
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1AUJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=PPB:'>PPB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AUJ OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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New inhibitors of thrombin and other trypsin-like proteases: hydrogen bonding of an aromatic cyano group with a backbone amide of the P1 binding site replaces binding of a basic side chain., Lee SL, Alexander RS, Smallwood A, Trievel R, Mersinger L, Weber PC, Kettner C, Biochemistry. 1997 Oct 28;36(43):13180-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9341205 9341205]
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</div>
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[[Category: Bos taurus]]
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<div class="pdbe-citations 1auj" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Trypsin]]
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[[Category: Alexander, R.]]
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[[Category: Kettner, C.]]
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[[Category: Smallwood, A.]]
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[[Category: CA]]
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[[Category: PPB]]
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[[Category: hydrolase]]
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[[Category: serine proteinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:48:25 2008''
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==See Also==
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*[[Trypsin 3D structures|Trypsin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Bos taurus]]
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[[Category: Large Structures]]
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[[Category: Alexander R]]
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[[Category: Kettner C]]
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[[Category: Smallwood A]]

Current revision

BOVINE TRYPSIN COMPLEXED TO META-CYANO-BENZYLIC INHIBITOR

PDB ID 1auj

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