View source for 3zcz


==Crystal structure of a complex between Actinomadura R39 DD-peptidase and a trifluoroketone inhibitor==
<StructureSection load='3zcz' size='340' side='right'caption='[[3zcz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zcz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinomadura_sp._R39 Actinomadura sp. R39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZCZ 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TFR:(2R)-2-AMINO-7-OXO-7-{[(2R,3S)-4,4,4-TRIFLUORO-3-HYDROXYBUTAN-2-YL]AMINO}HEPTANOIC+ACID'>TFR</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=3zcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zcz OCA], [https://pdbe.org/3zcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zcz RCSB], [https://www.ebi.ac.uk/pdbsum/3zcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zcz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAC_ACTSP DAC_ACTSP] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibitors of bacterial dd-peptidases represent potential antibiotics. In the search for alternatives to beta-lactams, we have investigated a series of compounds designed to generate transition state analogue structures upon reaction with dd-peptidases. The compounds contain a combination of a peptidoglycan-mimetic specificity handle and a warhead capable of delivering a tetrahedral anion to the enzyme active site. The latter includes a boronic acid, two alcohols, an aldehyde, and a trifluoroketone. The compounds were tested against two low-molecular mass class C dd-peptidases. As expected from previous observations, the boronic acid was a potent inhibitor, but rather unexpectedly from precedent, the trifluoroketone [d-alpha-aminopimelyl(1,1,1-trifluoro-3-amino)butan-2-one] was also very effective. Taking into account competing hydration, we found the trifluoroketone was the strongest inhibitor of the Actinomadura R39 dd-peptidase, with a subnanomolar (free ketone) inhibition constant. A crystal structure of the complex between the trifluoroketone and the R39 enzyme showed that a tetrahedral adduct had indeed formed with the active site serine nucleophile. The trifluoroketone moiety, therefore, should be considered along with boronic acids and phosphonates as a warhead that can be incorporated into new and effective dd-peptidase inhibitors and therefore, perhaps, antibiotics.

Inhibition of dd-Peptidases by a Specific Trifluoroketone: Crystal Structure of a Complex with the Actinomadura R39 dd-Peptidase.,Dzhekieva L, Adediran SA, Herman R, Kerff F, Duez C, Charlier P, Sauvage E, Pratt RF Biochemistry. 2013 Mar 13. PMID:23484909<ref>PMID:23484909</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zcz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Actinomadura sp. R39]]
[[Category: Large Structures]]
[[Category: Charlier P]]
[[Category: Herman R]]
[[Category: Kerff F]]
[[Category: Rocaboy M]]
[[Category: Sauvage E]]