4d2o: Difference between revisions
m Protected "4d2o" [edit=sysop:move=sysop] |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of the class A extended-spectrum beta-lactamase PER- 2== | ==Crystal structure of the class A extended-spectrum beta-lactamase PER- 2== | ||
<StructureSection load='4d2o' size='340' side='right' caption='[[4d2o]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='4d2o' size='340' side='right'caption='[[4d2o]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4d2o]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3znw 3znw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D2O OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4d2o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_freundii Citrobacter freundii]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3znw 3znw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D2O FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4d2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2o OCA], [https://pdbe.org/4d2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d2o RCSB], [https://www.ebi.ac.uk/pdbsum/4d2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d2o ProSAT]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A2RP81_CITFR A2RP81_CITFR] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PER-2 belongs to a small (7 members to date) group of extended-spectrum beta-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies towards most beta-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 A, and evaluated the possible role of several residues in the structure and activity towards beta-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular trans bond between residues 166-167 that generates an inverted Omega loop, and an expanded fold of this domain that results in a wide active site cavity that allows for an efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A beta-lactamases. PER beta-lactamases could be included within a cluster of evolutionary related enzymes harboring conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A, with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different beta-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-Water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we could expect that mutations occurring in these positions will have impact in the overall hydrolytic behavior. | |||
Crystal Structure of the Extended-Spectrum beta-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with beta-Lactams and beta-Lactamase Inhibitors.,Ruggiero M, Kerff F, Herman R, Sapunaric F, Galleni M, Gutkind G, Charlier P, Sauvage E, Power P Antimicrob Agents Chemother. 2014 Jul 28. pii: AAC.00089-14. PMID:25070104<ref>PMID:25070104</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4d2o" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Citrobacter freundii]] | ||
[[Category: Charlier | [[Category: Large Structures]] | ||
[[Category: Galleni | [[Category: Charlier P]] | ||
[[Category: Gutkind | [[Category: Galleni M]] | ||
[[Category: Herman | [[Category: Gutkind G]] | ||
[[Category: Kerff | [[Category: Herman R]] | ||
[[Category: Power | [[Category: Kerff F]] | ||
[[Category: Ruggiero | [[Category: Power P]] | ||
[[Category: Sauvage | [[Category: Ruggiero M]] | ||
[[Category: Sauvage E]] | |||
Latest revision as of 15:19, 20 December 2023
Crystal structure of the class A extended-spectrum beta-lactamase PER- 2Crystal structure of the class A extended-spectrum beta-lactamase PER- 2
Structural highlights
FunctionPublication Abstract from PubMedPER-2 belongs to a small (7 members to date) group of extended-spectrum beta-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies towards most beta-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 A, and evaluated the possible role of several residues in the structure and activity towards beta-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular trans bond between residues 166-167 that generates an inverted Omega loop, and an expanded fold of this domain that results in a wide active site cavity that allows for an efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A beta-lactamases. PER beta-lactamases could be included within a cluster of evolutionary related enzymes harboring conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A, with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different beta-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-Water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we could expect that mutations occurring in these positions will have impact in the overall hydrolytic behavior. Crystal Structure of the Extended-Spectrum beta-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with beta-Lactams and beta-Lactamase Inhibitors.,Ruggiero M, Kerff F, Herman R, Sapunaric F, Galleni M, Gutkind G, Charlier P, Sauvage E, Power P Antimicrob Agents Chemother. 2014 Jul 28. pii: AAC.00089-14. PMID:25070104[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||