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| - | [[Image:1tqq.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1tqq| PDB=1tqq | SCENE= }} | | {{STRUCTURE_1tqq| PDB=1tqq | SCENE= }} |
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| - | '''Structure of TolC in complex with hexamminecobalt'''
| + | ===Structure of TolC in complex with hexamminecobalt=== |
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| - | ==Overview==
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| - | The trimeric TolC protein of Escherichia coli comprises an outer membrane beta-barrel and a contiguous alpha-helical barrel projecting across the periplasm. This provides a single 140 A long pore for multidrug efflux and protein export. We have previously reported that trivalent cations such as hexammine cobalt can severely inhibit the conductivity of the TolC pore reconstituted in planar lipid bilayers. Here, isothermal calorimetry shows that Co(NH(3))(6)(3+) binds to TolC with an affinity of 20 nM. The crystal structure of the TolC-Co(NH(3))(6)(3+) complex was determined to 2.75 A resolution, and showed no significant difference in the protein when compared with unliganded TolC. An electron density difference map revealed that a single ligand molecule binds at the centre of the periplasmic entrance, the sole constriction of TolC. The octahedral symmetry of the ligand and the three-fold rotational symmetry of the TolC entrance determine a binding site in which the ligand forms hydrogen bonds with the Asp(374) residue of each monomer. When Asp(374) was substituted by alanine, high affinity ligand binding was abolished and inhibition of TolC pore conductivity in lipid bilayers was alleviated. Comparable effects followed independent substitution of the neighbouring Asp(371), indicating that this aspartate ring also contributes to the high affinity ligand binding site. As the electronegative entrance is widely conserved in the TolC family, it may be a useful target for the development of inhibitors against multidrug resistant pathogenic bacteria.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15342230}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15342230 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15342230}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Alpha-barrel]] | | [[Category: Alpha-barrel]] |
| | [[Category: Beta-barrel]] | | [[Category: Beta-barrel]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:15:49 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:43:39 2008'' |
Revision as of 02:43, 28 July 2008
Template:STRUCTURE 1tqq
Structure of TolC in complex with hexamminecobalt
Template:ABSTRACT PUBMED 15342230
About this Structure
1TQQ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structure of the ligand-blocked periplasmic entrance of the bacterial multidrug efflux protein TolC., Higgins MK, Eswaran J, Edwards P, Schertler GF, Hughes C, Koronakis V, J Mol Biol. 2004 Sep 17;342(3):697-702. PMID:15342230
Page seeded by OCA on Mon Jul 28 05:43:39 2008
