1uwf

From Proteopedia

(Difference between revisions)

Revision as of 13:01, 13 December 2023

1.7 A resolution structure of the receptor binding domain of the FimH adhesin from uropathogenic E. coli

Structural highlights

1uwf is a 1 chain structure with sequence from Escherichia coli J96. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.69Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol Microbiol. 2005 Jan;55(2):441-55. PMID:15659162 doi:10.1111/j.1365-2958.2004.04415.x

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1uwf"

@@ Line 3: / Line 3: @@
 <StructureSection load='1uwf' size='340' side='right'caption='[[1uwf]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1uwf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_j96 Escherichia coli j96]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UWF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1uwf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_J96 Escherichia coli J96]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UWF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DEG:BUTYL+ALPHA-D-MANNOPYRANOSIDE'>DEG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kiu|1kiu]], [[1klf|1klf]], [[1qun|1qun]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DEG:BUTYL+ALPHA-D-MANNOPYRANOSIDE'>DEG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uwf OCA], [https://pdbe.org/1uwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uwf RCSB], [https://www.ebi.ac.uk/pdbsum/1uwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uwf ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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.
+[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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli j96]]
+[[Category: Escherichia coli J96]]
 [[Category: Large Structures]]
-[[Category: Berglund, J]]
+[[Category: Berglund J]]
-[[Category: Bouckaert, J]]
+[[Category: Bouckaert J]]
-[[Category: Cools, L]]
+[[Category: Cools L]]
-[[Category: Genst, E D]]
+[[Category: De Greve H]]
-[[Category: Greve, H De]]
+[[Category: Genst ED]]
-[[Category: Hultgren, S]]
+[[Category: Hultgren S]]
-[[Category: Hung, C S]]
+[[Category: Hung C-S]]
-[[Category: Knight, S D]]
+[[Category: Knight SD]]
-[[Category: Langermann, S]]
+[[Category: Langermann S]]
-[[Category: Oscarson, S]]
+[[Category: Oscarson S]]
-[[Category: Wuhrer, M]]
+[[Category: Wuhrer M]]
-[[Category: Wyns, L]]
+[[Category: Wyns L]]
-[[Category: Zavialov, A]]
+[[Category: Zavialov A]]
-[[Category: Adherence to mammalian cell]]
-[[Category: Bacterial adhesin]]
-[[Category: Carbohydrate recognition]]
-[[Category: Cell adhesion]]
-[[Category: Ig-variable fold]]

1uwf

From Proteopedia

Revision as of 13:01, 13 December 2023

1.7 A resolution structure of the receptor binding domain of the FimH adhesin from uropathogenic E. coli

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox