1rcj

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[[Image:1rcj.jpg|left|200px]]
 
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==Crystal structure of E166A mutant of SHV-1 beta-lactamase with the trans-enamine intermediate of tazobactam==
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The line below this paragraph, containing "STRUCTURE_1rcj", creates the "Structure Box" on the page.
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<StructureSection load='1rcj' size='340' side='right'caption='[[1rcj]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1rcj]] is a 1 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=1RCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RCJ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.63&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TBI:TAZOBACTAM+TRANS-ENAMINE+INTERMEDIATE'>TBI</scene></td></tr>
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{{STRUCTURE_1rcj| PDB=1rcj | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rcj OCA], [https://pdbe.org/1rcj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rcj RCSB], [https://www.ebi.ac.uk/pdbsum/1rcj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rcj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rc/1rcj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1rcj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Many pathogenic bacteria develop antibiotic resistance by utilizing beta-lactamases to degrade penicillin-like antibiotics. A commonly prescribed mechanism-based inhibitor of beta-lactamases is tazobactam, which can function either irreversibly or in a transient manner. We have demonstrated previously that the reaction between tazobactam and a deacylation deficient variant of SHV-1 beta-lactamase, E166A, could be followed in single crystals using Raman microscopy [Helfand, M. S., et al. (2003) Biochemistry 42, 13386-13392]. The Raman data show that maximal populations of an enamine-like intermediate occur 20-30 min after "soaking in" has commenced. By flash-freezing crystals in this time frame, we were able to trap the enamine species. The resulting 1.63 A resolution crystal structure revealed tazobactam covalently bound in the trans-enamine intermediate state with close to 100% occupancy in the active site. The Raman data also indicated that tazobactam forms a larger population of enamine than sulbactam or clavulanic acid does and that tazobactam's intermediate is also the most long-lived. The crystal structure provides a rationale for this finding since only tazobactam is able to form favorable intra- and intermolecular interactions in the active site that stabilize this trans-enamine intermediate. These interactions involve both the sulfone and triazolyl groups that distinguish tazobactam from clavulanic acid and sulbactam, respectively. The observed stabilization of the transient intermediate of tazobactam is thought to contribute to tazobactam's superior in vitro and in vivo clinical efficacy. Understanding the structural details of differing inhibitor effectiveness can aid the design of improved mechanism-based beta-lactamase inhibitors.
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'''Crystal structure of E166A mutant of SHV-1 beta-lactamase with the trans-enamine intermediate of tazobactam'''
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Tazobactam forms a stoichiometric trans-enamine intermediate in the E166A variant of SHV-1 beta-lactamase: 1.63 A crystal structure.,Padayatti PS, Helfand MS, Totir MA, Carey MP, Hujer AM, Carey PR, Bonomo RA, van den Akker F Biochemistry. 2004 Feb 3;43(4):843-8. PMID:14744126<ref>PMID:14744126</ref>
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==Overview==
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Many pathogenic bacteria develop antibiotic resistance by utilizing beta-lactamases to degrade penicillin-like antibiotics. A commonly prescribed mechanism-based inhibitor of beta-lactamases is tazobactam, which can function either irreversibly or in a transient manner. We have demonstrated previously that the reaction between tazobactam and a deacylation deficient variant of SHV-1 beta-lactamase, E166A, could be followed in single crystals using Raman microscopy [Helfand, M. S., et al. (2003) Biochemistry 42, 13386-13392]. The Raman data show that maximal populations of an enamine-like intermediate occur 20-30 min after "soaking in" has commenced. By flash-freezing crystals in this time frame, we were able to trap the enamine species. The resulting 1.63 A resolution crystal structure revealed tazobactam covalently bound in the trans-enamine intermediate state with close to 100% occupancy in the active site. The Raman data also indicated that tazobactam forms a larger population of enamine than sulbactam or clavulanic acid does and that tazobactam's intermediate is also the most long-lived. The crystal structure provides a rationale for this finding since only tazobactam is able to form favorable intra- and intermolecular interactions in the active site that stabilize this trans-enamine intermediate. These interactions involve both the sulfone and triazolyl groups that distinguish tazobactam from clavulanic acid and sulbactam, respectively. The observed stabilization of the transient intermediate of tazobactam is thought to contribute to tazobactam's superior in vitro and in vivo clinical efficacy. Understanding the structural details of differing inhibitor effectiveness can aid the design of improved mechanism-based beta-lactamase inhibitors.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1RCJ is a [[Single protein]] structure of 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=1RCJ OCA].
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</div>
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<div class="pdbe-citations 1rcj" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Tazobactam forms a stoichiometric trans-enamine intermediate in the E166A variant of SHV-1 beta-lactamase: 1.63 A crystal structure., Padayatti PS, Helfand MS, Totir MA, Carey MP, Hujer AM, Carey PR, Bonomo RA, van den Akker F, Biochemistry. 2004 Feb 3;43(4):843-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14744126 14744126]
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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[[Category: Beta-lactamase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Klebsiella pneumoniae]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Akker, F van den.]]
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[[Category: Bonomo RA]]
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[[Category: Bonomo, R A.]]
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[[Category: Carey MP]]
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[[Category: Carey, M P.]]
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[[Category: Carey PR]]
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[[Category: Carey, P R.]]
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[[Category: Helfand MS]]
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[[Category: Helfand, M S.]]
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[[Category: Hujer AM]]
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[[Category: Hujer, A M.]]
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[[Category: Padayatti PS]]
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[[Category: Padayatti, P S.]]
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[[Category: Totir MA]]
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[[Category: Totir, M A.]]
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[[Category: Van den Akker F]]
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[[Category: Beta-lactam hydrolase]]
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[[Category: Beta-lactamase]]
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[[Category: Covalent intermediate]]
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[[Category: Detergent binding]]
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[[Category: Inhibitor design]]
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[[Category: Penicillinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:20:09 2008''
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Current revision

Crystal structure of E166A mutant of SHV-1 beta-lactamase with the trans-enamine intermediate of tazobactam

PDB ID 1rcj

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