View source for 2bfz

==BACILLUS CEREUS METALLO-BETA-LACTAMASE (BCII) ARG (121) CYS MUTANT. SOLVED AT PH4.5 USING 20MM ZNSO4 IN BUFFER. 1MM DTT WAS USED AS A REDUCING AGENT. CYS221 IS OXIDIZED.==
<StructureSection load='2bfz' size='340' side='right' caption='[[2bfz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bfz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BFZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BFZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bc2|1bc2]], [[1bmc|1bmc]], [[1bvt|1bvt]], [[1dxk|1dxk]], [[1mqo|1mqo]], [[2bc2|2bc2]], [[2bfk|2bfk]], [[2bfl|2bfl]], [[2bg2|2bg2]], [[2bg6|2bg6]], [[2bg7|2bg7]], [[2bg8|2bg8]], [[2bga|2bga]], [[3bc2|3bc2]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='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=2bfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bfz OCA], [http://pdbe.org/2bfz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bfz RCSB], [http://www.ebi.ac.uk/pdbsum/2bfz PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/BLA2_BACCE BLA2_BACCE]] 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/bf/2bfz_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The zinc-dependent metallo-beta-lactamases are a group of bacterial enzymes that pose a threat to the future efficacy of present-day antibiotics. Their mechanism is poorly understood, and there are no clinically useful inhibitors. While most members of the group contain two tightly bound zinc ions in their active sites, the Bacillus cereus enzyme has a much lower affinity for its second zinc (Zn2), thought to be due to the presence of Arg121 immediately beneath the floor of the active site (cf. Cys/Ser/His121 in the bizinc enzymes). Crystal structures of the Arg121Cys mutant of the B. cereus 569/H/9 enzyme were solved at pH 7.0, 5.0, and 4.5, each in the presence of either 20 microM or 20 mM Zn(2+) to generate the mono- and bizinc forms, respectively. Surprisingly, the structure of the active site was unaffected by the mutation; a network of ordered water molecules replaced the interactions made by the arginine side chain, and the occupancy of Zn2 appeared minimally changed. As the pH was lowered, Zn2 moved away from one of its ligands, Asp120, but was "tracked" by two others, Cys221 and His263. Furthermore, the hydroxide ion (and proposed nucleophile for beta-lactam hydrolysis) was bound to Zn1 at pH 5 and above but absent at pH 4.5. This provides experimental evidence for an earlier proposed mechanism in which protonation of Asp120 and the Zn1-bound hydroxide are the two events that lead to the loss of activity at low pH.

Effect of pH on the active site of an Arg121Cys mutant of the metallo-beta-lactamase from Bacillus cereus: implications for the enzyme mechanism.,Davies AM, Rasia RM, Vila AJ, Sutton BJ, Fabiane SM Biochemistry. 2005 Mar 29;44(12):4841-9. PMID:15779910<ref>PMID:15779910</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 2bfz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase|Beta-lactamase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Atcc 14579]]
[[Category: Beta-lactamase]]
[[Category: Davies, A M]]
[[Category: Fabiane, S M]]
[[Category: Rasia, R M]]
[[Category: Sutton, B J]]
[[Category: Vila, A J]]
[[Category: Antibiotic resistance]]
[[Category: Hydrolase]]