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| | ==GES-1 beta-lactamase== | | ==GES-1 beta-lactamase== |
| - | <StructureSection load='2qpn' size='340' side='right' caption='[[2qpn]], [[Resolution|resolution]] 1.10Å' scene=''> | + | <StructureSection load='2qpn' size='340' side='right'caption='[[2qpn]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qpn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QPN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QPN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qpn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QPN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ges-1, blaGES-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 Klebsiella pneumoniae])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qpn OCA], [http://pdbe.org/2qpn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qpn RCSB], [http://www.ebi.ac.uk/pdbsum/2qpn PDBsum]</span></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=2qpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qpn OCA], [https://pdbe.org/2qpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qpn RCSB], [https://www.ebi.ac.uk/pdbsum/2qpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qpn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BLAG1_KLEPN BLAG1_KLEPN] Extended-spectrum beta-lactamase (ESBL) which confers resistance to penicillins, as well as first, second, third and fourth-generation cephalosporins (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Has ceftazidime-hydrolyzing activity (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Inactive against the carbapenems, imipenem, meropenem, ertapenem and doripenem (PubMed:10681329, PubMed:19656947, PubMed:29507065). However, weak hydrolytic activity with respect to imipenem has also been reported (PubMed:20696873).<ref>PMID:10681329</ref> <ref>PMID:12936982</ref> <ref>PMID:19656947</ref> <ref>PMID:20696873</ref> <ref>PMID:29507065</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qp/2qpn_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qp/2qpn_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=2qpn ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-lactamase|Beta-lactamase]] | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Klebsiella pneumoniae]] | | [[Category: Klebsiella pneumoniae]] |
| - | [[Category: Caccamo, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Kantardjieff, K A]] | + | [[Category: Caccamo M]] |
| - | [[Category: Smith, C A]] | + | [[Category: Kantardjieff KA]] |
| - | [[Category: Vakulenko, S]] | + | [[Category: Smith CA]] |
| - | [[Category: Apo-enzyme]] | + | [[Category: Vakulenko S]] |
| - | [[Category: Beta-lactamase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
BLAG1_KLEPN Extended-spectrum beta-lactamase (ESBL) which confers resistance to penicillins, as well as first, second, third and fourth-generation cephalosporins (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Has ceftazidime-hydrolyzing activity (PubMed:10681329, PubMed:12936982, PubMed:19656947, PubMed:20696873, PubMed:29507065). Inactive against the carbapenems, imipenem, meropenem, ertapenem and doripenem (PubMed:10681329, PubMed:19656947, PubMed:29507065). However, weak hydrolytic activity with respect to imipenem has also been reported (PubMed:20696873).[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The structure of the class A extended-spectrum beta-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 A resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of beta-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the beta-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A beta-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of beta-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.
Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases.,Smith CA, Caccamo M, Kantardjieff KA, Vakulenko S Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):982-92. Epub 2007, Aug 17. PMID:17704567[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P. Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Antimicrob Agents Chemother. 2000 Mar;44(3):622-32. PMID:10681329 doi:10.1128/AAC.44.3.622-632.2000
- ↑ Correia M, Boavida F, Grosso F, Salgado MJ, Lito LM, Cristino JM, Mendo S, Duarte A. Molecular characterization of a new class 3 integron in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2003 Sep;47(9):2838-43. PMID:12936982 doi:10.1128/AAC.47.9.2838-2843.2003
- ↑ Frase H, Shi Q, Testero SA, Mobashery S, Vakulenko SB. Mechanistic basis for the emergence of catalytic competence against carbapenem antibiotics by the GES family of beta-lactamases. J Biol Chem. 2009 Oct 23;284(43):29509-13. PMID:19656947 doi:10.1074/jbc.M109.011262
- ↑ Kotsakis SD, Miriagou V, Tzelepi E, Tzouvelekis LS. Comparative biochemical and computational study of the role of naturally occurring mutations at Ambler positions 104 and 170 in GES β-lactamases. Antimicrob Agents Chemother. 2010 Nov;54(11):4864-71. PMID:20696873 doi:10.1128/AAC.00771-10
- ↑ Piccirilli A, Mercuri PS, Galleni M, Aschi M, Matagne A, Amicosante G, Perilli M. P174E Substitution in GES-1 and GES-5 β-Lactamases Improves Catalytic Efficiency toward Carbapenems. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e01851-17. PMID:29507065 doi:10.1128/AAC.01851-17
- ↑ Smith CA, Caccamo M, Kantardjieff KA, Vakulenko S. Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases. Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):982-92. Epub 2007, Aug 17. PMID:17704567 doi:10.1107/S0907444907036955
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