1kiu: Difference between revisions
New page: left|200px<br /><applet load="1kiu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kiu, resolution 3.0Å" /> '''FimH adhesin Q133N mu... |
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[[Image:1kiu.gif|left|200px]]<br /><applet load="1kiu" size=" | [[Image:1kiu.gif|left|200px]]<br /><applet load="1kiu" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1kiu, resolution 3.0Å" /> | caption="1kiu, resolution 3.0Å" /> | ||
'''FimH adhesin Q133N mutant-FimC chaperone complex with methyl-alpha-D-mannose'''<br /> | '''FimH adhesin Q133N mutant-FimC chaperone complex with methyl-alpha-D-mannose'''<br /> | ||
==Overview== | ==Overview== | ||
The first step in the colonization of the human urinary tract by | The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract. | ||
==About this Structure== | ==About this Structure== | ||
1KIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MMA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1KIU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MMA:'>MMA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KIU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bouckaert, J.]] | [[Category: Bouckaert, J.]] | ||
[[Category: Hung, C | [[Category: Hung, C S.]] | ||
[[Category: MMA]] | [[Category: MMA]] | ||
[[Category: adhesin-chaperone complex]] | [[Category: adhesin-chaperone complex]] | ||
[[Category: mannose-bound]] | [[Category: mannose-bound]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:34:40 2008'' | ||
Revision as of 14:34, 21 February 2008
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FimH adhesin Q133N mutant-FimC chaperone complex with methyl-alpha-D-mannose
OverviewOverview
The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract.
About this StructureAbout this Structure
1KIU is a Protein complex structure of sequences from Escherichia coli with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection., Hung CS, Bouckaert J, Hung D, Pinkner J, Widberg C, DeFusco A, Auguste CG, Strouse R, Langermann S, Waksman G, Hultgren SJ, Mol Microbiol. 2002 May;44(4):903-15. PMID:12010488
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