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[[ | ==Q157A mutant. Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157== | ||
<StructureSection load='4ax0' size='340' side='right' caption='[[4ax0]], [[Resolution|resolution]] 1.74Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ax0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AX0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AX0 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4awy|4awy]], [[4awz|4awz]], [[4ax1|4ax1]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ax0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ax0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ax0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ax0 PDBsum]</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> | |||
==See Also== | |||
*[[Beta-lactamase|Beta-lactamase]] | |||
== | == References == | ||
[[ | <references/> | ||
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== | </StructureSection> | ||
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[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Borra, P S.]] | [[Category: Borra, P S.]] | ||