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| - | [[Image:1znb.gif|left|200px]] | |
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| - | {{Structure
| + | ==METALLO-BETA-LACTAMASE== |
| - | |PDB= 1znb |SIZE=350|CAPTION= <scene name='initialview01'>1znb</scene>, resolution 1.85Å
| + | <StructureSection load='1znb' size='340' side='right'caption='[[1znb]], [[Resolution|resolution]] 1.85Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | + | <table><tr><td colspan='2'>[[1znb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZNB FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| - | |GENE= CCRA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=817 Bacteroides fragilis])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1znb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1znb OCA], [https://pdbe.org/1znb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1znb RCSB], [https://www.ebi.ac.uk/pdbsum/1znb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1znb ProSAT]</span></td></tr> |
| - | |RELATEDENTRY= | + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1znb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1znb OCA], [http://www.ebi.ac.uk/pdbsum/1znb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1znb RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/BLAB_BACFG BLAB_BACFG] Can hydrolyze carbapenem compounds. |
| | + | == 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/zn/1znb_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1znb ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''METALLO-BETA-LACTAMASE'''
| + | ==See Also== |
| - | | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | BACKGROUND: The metallo-beta-lactamase from Bacteroides fragilis hydrolyzes a wide range of beta-lactam antibiotics, and is not clinically susceptible to any known beta-lactamase inhibitors. B. fragilis is associated with post-surgery hospital infections, and there has been a recent report of plasmid-mediated dissemination of the enzyme. Effective inhibitors are therefore urgently needed. Knowledge of the three-dimensional structure will aid in the drug design effort. RESULTS: The crystal structure of the enzyme has been determined by using multiwavelength anomalous diffraction at the zinc absorption edge and refined to 1.85 A resolution. The structure is a four-layer alpha/beta/beta/alpha molecule. The active site, found at the edge of the beta sandwich contains a binuclear zinc center with several novel features. One zinc is tetrahedrally coordinated, the other has a trigonal bipyramidal coordination; a water/hydroxide molecule serves as a ligand for both metals. The residues that coordinate the two zincs are invariant in all metallo-beta-lactamases that have been sequenced, except for two conservative replacements. Despite the existence of the pattern for binuclear zinc binding, the reported structure of the Bacillus cereus enzyme contains only a single zinc. CONCLUSIONS: Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure. Models of bound substrates suggest that the active-site channel can accommodate a wide variety of beta-lactams. We propose that the zinc cluster prepares an hydroxide, probably the hydroxide that ligates both zincs, for nucleophilic attack on the carbonyl carbon atom of the beta-lactam. The resulting negatively charged tetrahedral intermediate implicated in catalysis is stabilized by an oxyanion hole formed by the side chain of the invariant Asn 193 and the tetrahedral zinc.
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| - | | + | |
| - | ==About this Structure==
| + | |
| - | 1ZNB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZNB OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | Crystal structure of the wide-spectrum binuclear zinc beta-lactamase from Bacteroides fragilis., Concha NO, Rasmussen BA, Bush K, Herzberg O, Structure. 1996 Jul 15;4(7):823-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8805566 8805566]
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| | [[Category: Bacteroides fragilis]] | | [[Category: Bacteroides fragilis]] |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Concha NO]] |
| - | [[Category: Concha, N O.]] | + | [[Category: Herzberg O]] |
| - | [[Category: Herzberg, O.]] | + | |
| - | [[Category: hydrolase (beta-lactamase)]]
| + | |
| - | [[Category: metallo beta-lactamase zinc]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:39:06 2008''
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