This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4de3

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:33, 14 March 2024) (edit) (undo)
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4de3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DE3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4de3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DE3 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DN8:3-BROMO-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>DN8</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.44&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DN8:3-BROMO-N-[3-(1H-TETRAZOL-5-YL)PHENYL]BENZAMIDE'>DN8</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4de3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4de3 OCA], [https://pdbe.org/4de3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4de3 RCSB], [https://www.ebi.ac.uk/pdbsum/4de3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4de3 ProSAT]</span></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=4de3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4de3 OCA], [https://pdbe.org/4de3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4de3 RCSB], [https://www.ebi.ac.uk/pdbsum/4de3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4de3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
-
[[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]]
+
[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 muM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design.
+
-
 
+
-
Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A beta-Lactamase.,Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y J Med Chem. 2012 Mar 8;55(5):2163-72. Epub 2012 Feb 14. PMID:22296601<ref>PMID:22296601</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4de3" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-
== References ==
 
-
<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

CTX-M-9 class A beta-lactamase complexed with compound 4

PDB ID 4de3

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4de3"
Personal tools