1llb
From Proteopedia
OCA (Talk | contribs)
(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...)
Next diff →
Revision as of 18:31, 20 November 2007
|
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 PCN 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
Page seeded by OCA on Tue Nov 20 20:39:02 2007
