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PDBsum entry 4lkd
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Sugar binding protein/inhibitor
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PDB id
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4lkd
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PDB id:
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| Name: |
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Sugar binding protein/inhibitor
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Title:
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Crystal structure of pseudomonas aeruginosa lectin leca complexed with gala-qrs at 2.31 a resolution
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Structure:
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Pa-i galactophilic lectin. Chain: a, b, c, d, e, f, g, h. Engineered: yes. Peptide qrsa. Chain: i, j, k, l, m, n, o, p. Engineered: yes
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Source:
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Pseudomonas aeruginosa. Organism_taxid: 208964. Strain: atcc 15692 / pao1 / 1c / prs 101 / lmg 12228. Gene: leca, pa1l, pa2570. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized.
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Resolution:
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2.31Å
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R-factor:
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0.216
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R-free:
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0.247
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Authors:
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R.U.Kadam,A.Stocker,J.-L.Reymond
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Key ref:
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R.U.Kadam
et al.
(2013).
Structure-based optimization of the terminal tripeptide in glycopeptide dendrimer inhibitors of Pseudomonas aeruginosa biofilms targeting LecA.
Chemistry,
19,
17054-17063.
PubMed id:
DOI:
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Date:
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07-Jul-13
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Release date:
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18-Dec-13
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PROCHECK
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Headers
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References
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Q05097
(PA1L_PSEAE) -
PA-I galactophilic lectin from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
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Seq:
Struc:
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122 a.a.
121 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Chemistry
19:17054-17063
(2013)
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PubMed id:
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Structure-based optimization of the terminal tripeptide in glycopeptide dendrimer inhibitors of Pseudomonas aeruginosa biofilms targeting LecA.
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R.U.Kadam,
M.Bergmann,
D.Garg,
G.Gabrieli,
A.Stocker,
T.Darbre,
J.L.Reymond.
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ABSTRACT
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The galactopeptide dendrimer GalAG2
((β-Gal-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2) binds strongly
to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as
well as disperses already established ones. By starting with the crystal
structure of the terminal tripeptide moiety GalA-KPL in complex with LecA, a
computational mutagenesis study was carried out on the galactotripeptide to
optimize the peptide-lectin interactions. 25 mutants were experimentally
evaluated by a hemagglutination inhibition assay, 17 by isothermal titration
calorimetry, and 3 by X-ray crystallography. Two of these tripeptides, GalA-KPY
(dissociation constant (K(D))=2.7 μM) and GalA-KRL (K(D)=2.7 μM), are among
the most potent monovalent LecA ligands reported to date. Dendrimers based on
these tripeptide ligands showed improved PA biofilm inhibition and dispersal
compared to those of GalAG2, particularly G2KPY
((β-Gal-OC6H4CO-Lys-Pro-Tyr)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2). The
possibility to retain and even improve the biofilm inhibition in several
analogues of GalAG2 suggests that it should be possible to fine-tune this
dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in
addition to the biofilm inhibition through amino acid substitutions.
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