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1llb
From Proteopedia
(New page: 200px<br /><applet load="1llb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1llb, resolution 1.72Å" /> '''Crystal Structure Of...) |
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| - | [[Image:1llb.gif|left|200px]]<br /><applet load="1llb" size=" | + | [[Image:1llb.gif|left|200px]]<br /><applet load="1llb" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1llb, resolution 1.72Å" /> | caption="1llb, resolution 1.72Å" /> | ||
'''Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With ATMO-penicillin'''<br /> | '''Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With ATMO-penicillin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | beta-lactamases confer resistance to beta-lactam antibiotics such as | + | beta-lactamases confer resistance to beta-lactam antibiotics such as penicillins and cephalosporins. However, beta-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of beta-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R(1) side chain of beta-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective beta-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design. |
==About this Structure== | ==About this Structure== | ||
| - | 1LLB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PCN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http:// | + | 1LLB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PCN:'>PCN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LLB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Blaszczak, L | + | [[Category: Blaszczak, L C.]] |
[[Category: Morandi, F.]] | [[Category: Morandi, F.]] | ||
| - | [[Category: Shoichet, B | + | [[Category: Shoichet, B K.]] |
[[Category: Trehan, I.]] | [[Category: Trehan, I.]] | ||
[[Category: PCN]] | [[Category: PCN]] | ||
| Line 24: | Line 24: | ||
[[Category: serine]] | [[Category: serine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:02 2008'' |
Revision as of 11:46, 21 February 2008
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Crystal Structure Of AmpC beta-Lactamase From E. Coli In Complex With ATMO-penicillin
Overview
beta-lactamases confer resistance to beta-lactam antibiotics such as penicillins and cephalosporins. However, beta-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of beta-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R(1) side chain of beta-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective beta-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.
About this Structure
1LLB is a Single protein structure of sequence from Escherichia coli with as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
Using steric hindrance to design new inhibitors of class C beta-lactamases., Trehan I, Morandi F, Blaszczak LC, Shoichet BK, Chem Biol. 2002 Sep;9(9):971-80. PMID:12323371
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