4d2o: Difference between revisions
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d2o RCSB], [http://www.ebi.ac.uk/pdbsum/4d2o PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4d2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d2o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d2o RCSB], [http://www.ebi.ac.uk/pdbsum/4d2o PDBsum]</span></td></tr> | ||
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== 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> | |||
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== References == | |||
<references/> | |||
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</StructureSection> | </StructureSection> | ||
Revision as of 09:15, 13 August 2014
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
Publication 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. References
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