2ntf: Difference between revisions
New page: left|200px<br /> <applet load="2ntf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ntf, resolution 3.18Å" /> '''Crystal Structure o... |
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'''Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog'''<br /> | '''Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2NTF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with OHM as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2NTF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=OHM:'>OHM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTF OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: quorum sensing]] | [[Category: quorum sensing]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:58:36 2008'' | ||
Revision as of 15:58, 23 January 2008
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Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog
OverviewOverview
A large number of Gram-negative bacteria employ N-acyl homoserine lactones, (AHLs) as signaling molecules in quorum sensing, which is a population, density-dependent mechanism to coordinate gene expression. Antibody, RS2-1G9 was elicited against a lactam mimetic of the N-acyl homoserine, lactone and represents the only reported monoclonal antibody that, recognizes the naturally-occuring N-acyl homoserine lactone with high, affinity. Due to its high cross-reactivity, RS2-1G9 showed remarkable, inhibition of quorum sensing signaling in Pseudomonas aeruginosa, a common, opportunistic pathogen in humans. The crystal structure of Fab RS2-1G9 in, complex with a lactam analog revealed complete encapsulation of the polar, lactam moiety in the antibody-combining site. This mode of recognition, provides an elegant immunological solution for tight binding to an, aliphatic, lipid-like ligand with a small head group lacking typical, haptenic features, such as aromaticity or charge, which are often, incorporated into hapten design to generate high-affinity antibodies. The, ability of RS2-1G9 to discriminate between closely related AHLs is, conferred by six hydrogen bonds to the ligand. Conversely, cross-reactivity of RS2-1G9 towards the lactone is likely to originate, from conservation of these hydrogen bonds as well as an additional, hydrogen bond to the oxygen of the lactone ring. A short, narrow tunnel, exiting at the protein surface harbors a portion of the acyl chain and, would not allow entry of the head group. The crystal structure of the, antibody without its cognate lactam or lactone ligands revealed a, considerably altered antibody-combining site with a closed binding pocket., Curiously, a completely buried ethylene glycol molecule mimics the lactam, ring and, thus, serves as a surrogate ligand. The detailed structural, delineation of this quorum-quenching antibody will aid further development, of an antibody-based therapy against bacterial pathogens by interference, with quorum sensing.
About this StructureAbout this Structure
2NTF is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal Structures of a Quorum-quenching Antibody., Debler EW, Kaufmann GF, Kirchdoerfer RN, Mee JM, Janda KD, Wilson IA, J Mol Biol. 2007 May 18;368(5):1392-402. Epub 2007 Mar 6. PMID:17400249
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