4awz
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4awz is ON HOLD Authors: Leiros, H.-K.S., Borra, P.S., Brandsdal, B.O., Edvardsen, K.S.W., Spencer, J., Walsh, T.R., Samuelsen, O. Description: Cry...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157== | |
| + | <StructureSection load='4awz' size='340' side='right'caption='[[4awz]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4awz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AWZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4awy|4awy]], [[4ax0|4ax0]], [[4ax1|4ax1]]</div></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=4awz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4awz OCA], [https://pdbe.org/4awz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4awz RCSB], [https://www.ebi.ac.uk/pdbsum/4awz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4awz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Metallo-beta-lactamase (MBL) genes confer resistance to virtually all beta-lactam antibiotics and are rapidly disseminated by mobile genetic elements in Gram-negative bacteria. MBLs belong to three different subgroups; B1, B2, and B3; with the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent subgroup of predominantly chromosomally encoded enzymes. AIM-1 (Adelaide IMipenmase) from Pseudomonas aeruginosa was the first B3 MBL to be identified on a readily mobile genetic element. Here we present the crystal structure of AIM-1, and use in silico docking and quantum and molecular mechanics (QM/MM) calculations, together with site-directed mutagenesis, to investigate its interaction with beta-lactams. AIM-1 adopts the characteristic alphabeta/betaalpha sandwich fold of MBLs, but differs from other B3 enzymes in the conformation of an active site loop (residues 156-162) which is involved both in disulfide bond formation and, we suggest, interaction with substrates. The structure, together with docking and QM/MM calculations, indicates that the AIM-1 substrate binding site is narrower and more restricted than those of other B3 MBLs, possibly explaining its higher catalytic efficiency. The location of Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is supported by our in silico studies, However, replacement of this residue by either Asn or Ala resulted in only modest reductions in AIM-1 activity against the majority of beta-lactam substrates, indicating that this function is non-essential. Our study reveals AIM-1 to be a subclass B3 MBL with novel structural and mechanistic features. | ||
| - | + | Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157.,Leiros HK, Borra PS, Brandsdal BO, Edvardsen KS, Spencer J, Walsh TR, Samuelsen O Antimicrob Agents Chemother. 2012 Jun 4. PMID:22664968<ref>PMID:22664968</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4awz" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Borra, P S]] | ||
| + | [[Category: Brandsdal, B O]] | ||
| + | [[Category: Edvardsen, K S.W]] | ||
| + | [[Category: Leiros, H K.S]] | ||
| + | [[Category: Samuelsen, O]] | ||
| + | [[Category: Spencer, J]] | ||
| + | [[Category: Walsh, T R]] | ||
| + | [[Category: Acquired b3]] | ||
| + | [[Category: Antibiotic resistance]] | ||
| + | [[Category: Drug binding site]] | ||
| + | [[Category: Hydrolase]] | ||
Current revision
Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157
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