5zfl: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 5zfl is ~~ON HOLD until Paper~~ Publication

==Crystal structure of beta-lactamase PenP mutant E166Y==

== Structural highlights ==

<table><tr><td colspan='2'>[[5zfl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZFL 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]] 1.5Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=5zfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zfl OCA], [https://pdbe.org/5zfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zfl RCSB], [https://www.ebi.ac.uk/pdbsum/5zfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zfl ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI]

== Publication Abstract from PubMed ==

Serine-based beta-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate beta-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the beta-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated beta-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A beta-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Burgi-Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent beta-lactamase-mediated antibiotic resistance.

~~Authors:~~ Pan, X., Zhao, Y.

The hydrolytic water molecule of Class A beta-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis.,He Y, Lei J, Pan X, Huang X, Zhao Y Sci Rep. 2020 Jun 23;10(1):10205. doi: 10.1038/s41598-020-66431-w. PMID:32576842<ref>PMID:32576842</ref>

~~Description~~: ~~Crystal structure of beta~~-lactamase ~~PenP mutant E166Y~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Pan, X]]

[[Category: Zhao, Y]]

==See Also==

*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Bacillus licheniformis]]

[[Category: Large Structures]]

[[Category: Pan X]]

[[Category: Zhao Y]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5zfl is ON HOLD  until Paper Publication
+==Crystal structure of beta-lactamase PenP mutant E166Y==
+<StructureSection load='5zfl' size='340' side='right'caption='[[5zfl]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5zfl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZFL 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]] 1.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=5zfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zfl OCA], [https://pdbe.org/5zfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zfl RCSB], [https://www.ebi.ac.uk/pdbsum/5zfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zfl ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Serine-based beta-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate beta-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the beta-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated beta-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A beta-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Burgi-Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent beta-lactamase-mediated antibiotic resistance.
-Authors: Pan, X., Zhao, Y.
+The hydrolytic water molecule of Class A beta-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis.,He Y, Lei J, Pan X, Huang X, Zhao Y Sci Rep. 2020 Jun 23;10(1):10205. doi: 10.1038/s41598-020-66431-w. PMID:32576842<ref>PMID:32576842</ref>
-Description: Crystal structure of beta-lactamase PenP mutant E166Y
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pan, X]]
+<div class="pdbe-citations 5zfl" style="background-color:#fffaf0;"></div>
-[[Category: Zhao, Y]]
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bacillus licheniformis]]
+[[Category: Large Structures]]
+[[Category: Pan X]]
+[[Category: Zhao Y]]