2i72: Difference between revisions

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[[Image:2i72.~~jpg~~|left|200px]]

[[Image:2i72.png|left|200px]]

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~~'''~~AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid~~'''~~

===AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid===

~~==Overview==~~

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~~Benzo[b]thiophene~~-2-~~ylboronic acid~~, 1, ~~is a 27 nM inhibitor of~~ the ~~class C beta-lactamase AmpC and potentiates~~ the ~~activity of beta-lactam antibiotics in bacteria that express this and related enzymes~~. ~~As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria~~, where ~~the minimum inhibitor concentration of compound 1~~ is in the ~~mid-micromolar range~~. ~~Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X~~-~~ray crystallography, structure~~-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.

The line below this paragraph, {{ABSTRACT_PUBMED_17956081}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 17956081 is the PubMed ID number.

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==About this Structure==

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[[Category: Cephalosporinase]]

[[Category: Serine hydrolase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May 4 07~~:09:38 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:15:01 2008''

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-[[Image:2i72.jpg|left|200px]]
+{{Seed}}
+[[Image:2i72.png|left|200px]]
 <!--
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 {{STRUCTURE_2i72|  PDB=2i72  |  SCENE=  }}
-'''AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid'''
+===AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid===
-==Overview==
+<!--
-Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.
+The line below this paragraph, {{ABSTRACT_PUBMED_17956081}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17956081 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_17956081}}
 ==About this Structure==
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 [[Category: Cephalosporinase]]
 [[Category: Serine hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:09:38 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:15:01 2008''