1xui

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[[Image:1xui.gif|left|200px]]
 
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==TRYPSIN-KETO-BABIM, ZN+2-FREE, PH 8.2==
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The line below this paragraph, containing "STRUCTURE_1xui", creates the "Structure Box" on the page.
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<StructureSection load='1xui' size='340' side='right'caption='[[1xui]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1xui]] 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=1XUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XUI FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.5&#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=BAO:BIS(5-AMIDINO-2-BENZIMIDAZOLYL)METHANONE'>BAO</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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{{STRUCTURE_1xui| PDB=1xui | SCENE= }}
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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=1xui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xui OCA], [https://pdbe.org/1xui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xui RCSB], [https://www.ebi.ac.uk/pdbsum/1xui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xui 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/xu/1xui_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1xui 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 ==
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Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.
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'''TRYPSIN-KETO-BABIM, ZN+2-FREE, PH 8.2'''
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Design of potent selective zinc-mediated serine protease inhibitors.,Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM Nature. 1998 Feb 5;391(6667):608-12. PMID:9468142<ref>PMID:9468142</ref>
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==Overview==
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Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1XUI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XUI OCA].
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</div>
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<div class="pdbe-citations 1xui" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Design of potent selective zinc-mediated serine protease inhibitors., Katz BA, Clark JM, Finer-Moore JS, Jenkins TE, Johnson CR, Ross MJ, Luong C, Moore WR, Stroud RM, Nature. 1998 Feb 5;391(6667):608-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9468142 9468142]
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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>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Trypsin]]
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[[Category: Clark JM]]
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[[Category: Clark, J M.]]
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[[Category: Finer-Moore JS]]
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[[Category: Finer-Moore, J S.]]
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[[Category: Jenkins TE]]
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[[Category: Jenkins, T E.]]
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[[Category: Johnson CR]]
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[[Category: Johnson, C R.]]
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[[Category: Katz BA]]
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[[Category: Katz, B A.]]
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[[Category: Luong C]]
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[[Category: Luong, C.]]
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[[Category: Moore WR]]
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[[Category: Moore, W R.]]
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[[Category: Rose MJ]]
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[[Category: Rose, M J.]]
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[[Category: Stroud RM]]
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[[Category: Stroud, R M.]]
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[[Category: Complex]]
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[[Category: Designed small molecule ligand with micromolar affinity]]
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[[Category: Trypsin-small molecule ligand]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:31:28 2008''
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Current revision

TRYPSIN-KETO-BABIM, ZN+2-FREE, PH 8.2

PDB ID 1xui

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