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| | <StructureSection load='4awy' size='340' side='right'caption='[[4awy]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='4awy' size='340' side='right'caption='[[4awy]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4awy]] is a 1 chain structure with sequence from [http://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=4AWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AWY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4awy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AWY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4awz|4awz]], [[4ax0|4ax0]], [[4ax1|4ax1]]</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='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=4awy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4awy OCA], [http://pdbe.org/4awy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4awy RCSB], [http://www.ebi.ac.uk/pdbsum/4awy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4awy ProSAT]</span></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=4awy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4awy OCA], [https://pdbe.org/4awy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4awy RCSB], [https://www.ebi.ac.uk/pdbsum/4awy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4awy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/B5DCA0_PSEAI B5DCA0_PSEAI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Borra, P S]] | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Brandsdal, B O]] | + | [[Category: Borra PS]] |
| - | [[Category: Edvardsen, K S.W]] | + | [[Category: Brandsdal BO]] |
| - | [[Category: Leiros, H K.S]] | + | [[Category: Edvardsen KSW]] |
| - | [[Category: Samuelsen, O]] | + | [[Category: Leiros H-KS]] |
| - | [[Category: Spencer, J]] | + | [[Category: Samuelsen O]] |
| - | [[Category: Walsh, T R]] | + | [[Category: Spencer J]] |
| - | [[Category: Acquired b3]]
| + | [[Category: Walsh TR]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Drug binding site]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Intramolecular disulphide bridge]]
| + | |
| Structural highlights
Function
B5DCA0_PSEAI
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Leiros HK, Borra PS, Brandsdal BO, Edvardsen KS, Spencer J, Walsh TR, Samuelsen O. Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157. Antimicrob Agents Chemother. 2012 Jun 4. PMID:22664968 doi:10.1128/AAC.00448-12
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