1tr7

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[[Image:1tr7.gif|left|200px]]
 
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{{Structure
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==FimH adhesin receptor binding domain from uropathogenic E. coli==
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|PDB= 1tr7 |SIZE=350|CAPTION= <scene name='initialview01'>1tr7</scene>, resolution 2.10&Aring;
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<StructureSection load='1tr7' size='340' side='right'caption='[[1tr7]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=DEG:BUTYL+ALPHA-D-MANNOPYRANOSIDE'>DEG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>
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<table><tr><td colspan='2'>[[1tr7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TR7 FirstGlance]. <br>
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|ACTIVITY=
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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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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=DEG:BUTYL+ALPHA-D-MANNOPYRANOSIDE'>DEG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
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|DOMAIN=
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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=1tr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tr7 OCA], [https://pdbe.org/1tr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tr7 RCSB], [https://www.ebi.ac.uk/pdbsum/1tr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tr7 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1uwf|1UWF]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tr7 OCA], [http://www.ebi.ac.uk/pdbsum/1tr7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tr7 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/FIMH_ECOLI FIMH_ECOLI] Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed.
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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/tr/1tr7_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=1tr7 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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Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl alpha-D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (Kd = 0.15 microM) than mannose (Kd = 2.3 microM). Exploration of the binding affinities of alpha- d-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.
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'''FimH adhesin receptor binding domain from uropathogenic E. coli'''
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Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin.,Bouckaert J, Berglund J, Schembri M, De Genst E, Cools L, Wuhrer M, Hung CS, Pinkner J, Slattegard R, Zavialov A, Choudhury D, Langermann S, Hultgren SJ, Wyns L, Klemm P, Oscarson S, Knight SD, De Greve H Mol Microbiol. 2005 Jan;55(2):441-55. PMID:15659162<ref>PMID:15659162</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1tr7" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl alpha-D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (Kd = 0.15 microM) than mannose (Kd = 2.3 microM). Exploration of the binding affinities of alpha- d-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.
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*[[Adhesin 3D structures|Adhesin 3D structures]]
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*[[Urease|Urease]]
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==About this Structure==
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== References ==
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1TR7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TR7 OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin., Bouckaert J, Berglund J, Schembri M, De Genst E, Cools L, Wuhrer M, Hung CS, Pinkner J, Slattegard R, Zavialov A, Choudhury D, Langermann S, Hultgren SJ, Wyns L, Klemm P, Oscarson S, Knight SD, De Greve H, Mol Microbiol. 2005 Jan;55(2):441-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15659162 15659162]
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Berglund, J.]]
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[[Category: Berglund J]]
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[[Category: Bouckaert, J.]]
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[[Category: Bouckaert J]]
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[[Category: Choudhury, D.]]
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[[Category: Choudhury D]]
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[[Category: Cools, L.]]
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[[Category: Cools L]]
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[[Category: Genst, E De.]]
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[[Category: De Genst E]]
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[[Category: Greve, H De.]]
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[[Category: De Greve H]]
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[[Category: Hultgren, S J.]]
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[[Category: Hultgren SJ]]
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[[Category: Hung, C S.]]
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[[Category: Hung CS]]
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[[Category: Klemm, P.]]
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[[Category: Klemm P]]
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[[Category: Knight, S D.]]
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[[Category: Knight SD]]
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[[Category: Langermann, S.]]
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[[Category: Langermann S]]
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[[Category: Oscarson, S.]]
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[[Category: Oscarson S]]
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[[Category: Pinkner, J.]]
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[[Category: Pinkner J]]
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[[Category: Schembri, M.]]
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[[Category: Schembri M]]
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[[Category: Slattegard, R.]]
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[[Category: Slattegard R]]
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[[Category: Wuhrer, M.]]
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[[Category: Wuhrer M]]
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[[Category: Wyns, L.]]
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[[Category: Wyns L]]
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[[Category: Zavialov, A.]]
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[[Category: Zavialov A]]
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[[Category: adhesion]]
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[[Category: carbohydrate binding]]
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[[Category: type-1 pili]]
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[[Category: urinary tract infection]]
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[[Category: uropathogenic e. coli]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:00:00 2008''
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Current revision

FimH adhesin receptor binding domain from uropathogenic E. coli

PDB ID 1tr7

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