View source for 1onh


==GC1 beta-lactamase with a penem inhibitor==
<StructureSection load='1onh' size='340' side='right'caption='[[1onh]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1onh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ONH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ONH 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]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=WY4:7-(5,6-DIHYDRO-8H-IMIDAZO[2,1-C][1,4]OXAZIN-2-YL)-6-FORMYL-2,7-DIHYDRO-+[1,4]THIAZEPINE-3-CARBOXYLIC+ACID'>WY4</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=1onh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1onh OCA], [https://pdbe.org/1onh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1onh RCSB], [https://www.ebi.ac.uk/pdbsum/1onh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1onh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q59401_ENTCL Q59401_ENTCL] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/on/1onh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=1onh ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A new beta-lactamase inhibitor, a methylidene penem having a 5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine heterocyclic substituent at the C6 position with a Z configuration, irreversibly inhibits both class A and class C serine beta-lactamases with IC(50) values of 0.4 and 9.0 nM for TEM-1 and SHV-1 (class A), respectively, and 4.8 nM in AmpC (class C) beta-lactamases. The compound also inhibits irreversibly the class C extended-spectrum GC1 beta-lactamase (IC(50) = 6.2 nM). High-resolution crystallographic structures of a reaction intermediate of (5R)-(6Z)-6-(5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-2-ylmethylene)-7-oxo -4-thia-1-azabicyclo[3.2.0]hept-2-ene-3-carboxylic acid 1 with the SHV-1 beta-lactamase and with the GC1 beta-lactamase have been determined by X-ray diffraction to resolutions of 1.10 and 1.38 A, respectively. The two complexes were refined to crystallographic R-factors (R(free)) of 0.141 (0.186) and 0.138 (0.202), respectively. Cryoquenching of the reaction of 1 with each beta-lactamase crystal produced a common, covalently bound intermediate. After acylation of the serine, a nucleophilic attack by the departing thiolate on the C6' atom yielded a novel seven-membered 1,4-thiazepine ring having R stereochemistry at the new C7 moiety. The orientation of this ring in each complex differs by a 180 degrees rotation about the bond to the acylated serine. The acyl ester bond is stabilized to hydrolysis through resonance stabilization with the dihydrothiazepine ring and by low occupancy or disorder of hydrolytic water molecules. In the class A complex, the buried water molecule on the alpha-face of the ester bond appears to be loosely bound or absent. In the class C complex, a water molecule on the beta-face is disordered and poorly activated for hydrolysis. Here, the acyl intermediate is unable to assist its own hydrolysis, as is thought to occur with many class C substrates.

Inhibition of class A and class C beta-lactamases by penems: crystallographic structures of a novel 1,4-thiazepine intermediate.,Nukaga M, Abe T, Venkatesan AM, Mansour TS, Bonomo RA, Knox JR Biochemistry. 2003 Nov 18;42(45):13152-9. PMID:14609325<ref>PMID:14609325</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1onh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterobacter cloacae]]
[[Category: Large Structures]]
[[Category: Knox JR]]
[[Category: Nukaga K]]
[[Category: Nukaga M]]