4ax0: Difference between revisions

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-[[Image:4ax0.jpg|left|200px]]
-{{STRUCTURE_4ax0|  PDB=4ax0  |  SCENE=  }}
+==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]] 1.74&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ax0]] 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=4AX0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AX0 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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'>[https://proteopedia.org/fgij/fg.htm?mol=4ax0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ax0 OCA], [https://pdbe.org/4ax0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ax0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ax0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ax0 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/B5DCA0_PSEAI B5DCA0_PSEAI]
+<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.
-===Q157A mutant. Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157===
+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>
-{{ABSTRACT_PUBMED_22664968}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ax0" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[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].
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:022664968</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Pseudomonas aeruginosa]]
-[[Category: Borra, P S.]]
+[[Category: Borra PS]]
-[[Category: Brandsdal, B O.]]
+[[Category: Brandsdal BO]]
-[[Category: Edvardsen, K S.W.]]
+[[Category: Edvardsen KSW]]
-[[Category: Leiros, H K.S.]]
+[[Category: Leiros H-KS]]
-[[Category: Samuelsen, O.]]
+[[Category: Samuelsen O]]
-[[Category: Spencer, J.]]
+[[Category: Spencer J]]
-[[Category: Walsh, T R.]]
+[[Category: Walsh TR]]
-[[Category: Acquired b3]]
-[[Category: Antibiotic resistance]]
-[[Category: Drug binding site]]
-[[Category: Hydrolase]]