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.


1my8

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1my8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1my8, resolution 1.72&Aring;" /> '''AmpC beta-lactamase ...)
Current revision (08:43, 10 April 2024) (edit) (undo)
 
(15 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1my8.jpg|left|200px]]<br /><applet load="1my8" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1my8, resolution 1.72&Aring;" />
 
-
'''AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain'''<br />
 
-
==Overview==
+
==AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain==
-
beta-lactamases are the most widespread resistance mechanism to, beta-lactam antibiotics, such as the penicillins and the cephalosporins., In an effort to combat these enzymes, a combination of stereoselective, organic synthesis, enzymology, microbiology, and X-ray crystallography was, used to design and evaluate new carboxyphenyl-glycylboronic acid, transition-state analogue inhibitors of the class C beta-lactamase AmpC., The new compounds improve inhibition by over 2 orders of magnitude, compared to analogous glycylboronic acids, with K(i) values as low as 1, nM. On the basis of the differential binding of different analogues, the, introduced carboxylate alone contributes about 2.1 kcal/mol in affinity., This carboxylate corresponds to the ubiquitous C3(4)' carboxylate of, beta-lactams, and this energy represents the first thermodynamic, measurement of the importance of this group in molecular recognition by, class C beta-lactamases. The structures of AmpC in complex with two of, these inhibitors were determined by X-ray crystallography at 1.72 and 1.83, A resolution. These structures suggest a structural basis for the high, affinity of the new compounds and provide templates for further design., The highest affinity inhibitor was 5 orders of magnitude more selective, for AmpC than for characteristic serine proteases, such as chymotrypsin., This inhibitor reversed the resistance of clinical pathogens to the third, generation cephalosporin ceftazidime; it may serve as a lead compound for, drug discovery to combat bacterial resistance to beta-lactam antibiotics.
+
<StructureSection load='1my8' size='340' side='right'caption='[[1my8]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1my8]] 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=1MY8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MY8 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]] 1.72&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SM3:(1R)-1-(2-THIENYLACETYLAMINO)-1-PHENYLMETHYLBORONIC+ACID'>SM3</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=1my8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1my8 OCA], [https://pdbe.org/1my8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1my8 RCSB], [https://www.ebi.ac.uk/pdbsum/1my8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1my8 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.
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/my/1my8_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1my8 ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1MY8 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 PO4 and SM3 as [http://en.wikipedia.org/wiki/ligands ligands]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MY8 OCA].
+
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
Nanomolar inhibitors of AmpC beta-lactamase., Morandi F, Caselli E, Morandi S, Focia PJ, Blazquez J, Shoichet BK, Prati F, J Am Chem Soc. 2003 Jan 22;125(3):685-95. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12526668 12526668]
+
-
[[Category: Beta-lactamase]]
+
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Blazquez, J.]]
+
[[Category: Blazquez J]]
-
[[Category: Caselli, E.]]
+
[[Category: Caselli E]]
-
[[Category: Focia, P.J.]]
+
[[Category: Focia PJ]]
-
[[Category: Morandi, F.]]
+
[[Category: Morandi F]]
-
[[Category: Morandi, S.]]
+
[[Category: Morandi S]]
-
[[Category: Prati, F.]]
+
[[Category: Prati F]]
-
[[Category: Shoichet, B.K.]]
+
[[Category: Shoichet BK]]
-
[[Category: PO4]]
+
-
[[Category: SM3]]
+
-
[[Category: ampc]]
+
-
[[Category: beta-lactamase]]
+
-
[[Category: cephalosporinase]]
+
-
[[Category: serine hydrolase]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:48:27 2007''
+

Current revision

AmpC beta-lactamase in complex with an M.carboxyphenylglycylboronic acid bearing the cephalothin R1 side chain

PDB ID 1my8

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/1my8"
Personal tools