2ntf: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2ntf.jpg|left|200px]] | [[Image:2ntf.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_2ntf", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_2ntf| PDB=2ntf | SCENE= }} | |||
}} | |||
'''Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog''' | '''Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog''' | ||
| Line 19: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTF OCA]. | |||
==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/17400249 17400249] | 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://www.ncbi.nlm.nih.gov/pubmed/17400249 17400249] | ||
[[Category: Debler, E W.]] | [[Category: Debler, E W.]] | ||
[[Category: Wilson, I A.]] | [[Category: Wilson, I A.]] | ||
[[Category: | [[Category: Antibody]] | ||
[[Category: | [[Category: Fab]] | ||
[[Category: | [[Category: Hapten complex]] | ||
[[Category: | [[Category: Homoserine lactone]] | ||
[[Category: | [[Category: Immunoglobulin]] | ||
[[Category: | [[Category: Quorum sensing]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:53:26 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 06:53, 4 May 2008
Crystal Structure of a Quorum-Quenching Antibody in Complex with an N-Acyl-L-Homoserine Lactone Analog
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
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 Sun May 4 09:53:26 2008
