4e3n: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:4e3n.png|left|200px]]
-{{STRUCTURE_4e3n|  PDB=4e3n  |  SCENE=  }}
+==Crystal structure of AmpC beta-lactamase in complex with a 2-trifluoromethyl-4-tetrazolyl benzene sulfonamide boronic acid inhibitor==
+<StructureSection load='4e3n' size='340' side='right'caption='[[4e3n]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4e3n]] 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=4E3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E3N 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]] 1.49&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NE:[({[4-(1H-TETRAZOL-5-YL)-2-(TRIFLUOROMETHYL)PHENYL]SULFONYL}AMINO)METHYL]BORONIC+ACID'>0NE</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=4e3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3n OCA], [https://pdbe.org/4e3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e3n RCSB], [https://www.ebi.ac.uk/pdbsum/4e3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e3n 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.
-===Crystal structure of AmpC beta-lactamase in complex with a 2-trifluoromethyl-4-tetrazolyl benzene sulfonamide boronic acid inhibitor===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4e3n" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[4e3n]] is a 2 chain structure with sequence from [http://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=4E3N OCA].
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-[[Category: Beta-lactamase]]
+== References ==
-[[Category: Escherichia coli k-12]]
+<references/>
-[[Category: Eidam, O.]]
+__TOC__
-[[Category: Shoichet, B K.]]
+</StructureSection>
-[[Category: Ampc beta-lactamase]]
+[[Category: Escherichia coli K-12]]
-[[Category: Cephalosporinase]]
+[[Category: Large Structures]]
-[[Category: Class c]]
+[[Category: Eidam O]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Shoichet BK]]