4e3l: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 4e3l is ON HOLD
+==Crystal structure of AmpC beta-lactamase in complex with a 3-chloro-4-tetrazolyl benzene sulfonamide boronic acid inhibitor==
+<StructureSection load='4e3l' size='340' side='right'caption='[[4e3l]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4e3l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E3L FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NB:[({[3-CHLORO-4-(1H-TETRAZOL-5-YL)PHENYL]SULFONYL}AMINO)METHYL]BORONIC+ACID'>0NB</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3l OCA], [https://pdbe.org/4e3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e3l RCSB], [https://www.ebi.ac.uk/pdbsum/4e3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e3l ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Fragment-based design was used to guide derivatization of a lead series of beta-lactamase inhibitors that had heretofore resisted optimization for in vivo activity. X-ray structures of fragments overlaid with the lead suggested new, unanticipated functionality and points of attachment. Synthesis of three derivatives improved affinity over 20-fold and improved efficacy in cell culture. Crystal structures were consistent with the fragment-based design, enabling further optimization to a K(i) of 50 pM, a 500-fold improvement that required the synthesis of only six derivatives. One of these, compound 5, was tested in mice. Whereas cefotaxime alone failed to cure mice infected with beta-lactamase-expressing Escherichia coli, 65% were cleared of infection when treated with a cefotaxime:5 combination. Fragment complexes offer a path around design hurdles, even for advanced molecules; the series described here may provide leads to overcome beta-lactamase-based resistance, a key clinical challenge.
-Authors: Eidam, O., Shoichet, B.K.
+Fragment-guided design of subnanomolar beta-lactamase inhibitors active in vivo.,Eidam O, Romagnoli C, Dalmasso G, Barelier S, Caselli E, Bonnet R, Shoichet BK, Prati F Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17448-53. doi:, 10.1073/pnas.1208337109. Epub 2012 Oct 5. PMID:23043117<ref>PMID:23043117</ref>
-Description: Crystal structure of AmpC beta-lactamase in complex with a 3-chloro-4-tetrazolyl benzene sulfonamide boronic acid inhibitor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4e3l" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli K-12]]
+[[Category: Large Structures]]
+[[Category: Eidam O]]
+[[Category: Shoichet BK]]