2op4
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | A large number of Gram-negative bacteria employ N-acyl homoserine lactones | + | 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 Structure== | ==About this Structure== | ||
| Line 10: | Line 10: | ||
==Reference== | ==Reference== | ||
| - | Crystal | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17400249 17400249] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Debler, E | + | [[Category: Debler, E W.]] |
| - | [[Category: Kirchdoerfer, R | + | [[Category: Kirchdoerfer, R N.]] |
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
| Line 24: | Line 24: | ||
[[Category: quorum sensing]] | [[Category: quorum sensing]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:00 2008'' |
Revision as of 16:21, 21 February 2008
|
Crystal Structure of Quorum-Quenching Antibody 1G9
Overview
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 Structure
2OP4 is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:21:00 2008
