This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4awy

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

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 3: / Line 3: @@
 <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/"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]] 1.6&#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://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>
+== Function ==
+[https://www.uniprot.org/uniprot/B5DCA0_PSEAI B5DCA0_PSEAI]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[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]]

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?)

Views

Personal tools

Navigation

Search

Toolbox