4awy

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157

Structural highlights

4awy is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4awy"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157==
-<StructureSection load='4awy' size='340' side='right' caption='[[4awy]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='4awy' size='340' side='right'caption='[[4awy]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4awy]] 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=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]] 1.6&#8491;</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://www.rcsb.org/pdb/explore.do?structureId=4awy RCSB], [http://www.ebi.ac.uk/pdbsum/4awy PDBsum]</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>
+== Function ==
+[https://www.uniprot.org/uniprot/B5DCA0_PSEAI B5DCA0_PSEAI]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4awy" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Beta-lactamase|Beta-lactamase]]
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 == References ==
 <references/>
 __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]]
-[[Category: Intramolecular disulphide bridge]]

4awy

From Proteopedia

Current revision

Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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