3lvz: Difference between revisions
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< | ==New refinement of the crystal structure of BJP-1, a subclass B3 metallo-beta-lactamase of Bradyrhizobium japonicum== | ||
<StructureSection load='3lvz' size='340' side='right'caption='[[3lvz]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3lvz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bradyrhizobium_diazoefficiens_USDA_110 Bradyrhizobium diazoefficiens USDA 110]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LVZ 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]] 1.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=3lvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lvz OCA], [https://pdbe.org/3lvz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lvz RCSB], [https://www.ebi.ac.uk/pdbsum/3lvz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lvz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q89GW5_BRADU Q89GW5_BRADU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Metallo-beta-lactamases (MBLs) are important enzymatic factors in resistance to beta-lactam antibiotics that show important structural and functional heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by Bradyrhizobium japonicum that exhibits interesting properties. BJP-1, like CAU-1 of Caulobacter vibrioides, overall poorly recognizes beta-lactam substrates and shows an unusual substrate profile compared to other MBLs. In order to understand the structural basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-A resolution. This revealed significant differences in the conformation and locations of the active-site loops, determining a rather narrow active site and the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds in the active site and represents an obstacle for beta-lactam substrate binding. In order to probe the potential of sulfonamides (known to inhibit various zinc-dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-A resolution), thereby revealing the mode of interaction of these molecules in MBLs. Interestingly, sulfonamide binding resulted in the displacement of the side chain of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the molecule is now found. These data further highlight the structural diversity shown by MBLs but also provide interesting insights in the structure-function relationships of these enzymes. More importantly, we provided the first structural observation of MBL interaction with sulfonamides, which might represent an interesting scaffold for the design of MBL inhibitors. | |||
High-resolution crystal structure of the subclass B3 metallo-beta-lactamase BJP-1: rational basis for substrate specificity and interaction with sulfonamides.,Docquier JD, Benvenuti M, Calderone V, Stoczko M, Menciassi N, Rossolini GM, Mangani S Antimicrob Agents Chemother. 2010 Oct;54(10):4343-51. Epub 2010 Aug 9. PMID:20696874<ref>PMID:20696874</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3lvz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Bradyrhizobium diazoefficiens USDA 110]] | ||
[[ | [[Category: Large Structures]] | ||
[[Category: Benvenuti M]] | |||
== | [[Category: Calderone V]] | ||
< | [[Category: Docquier JD]] | ||
[[Category: Bradyrhizobium | [[Category: Mangani S]] | ||
[[Category: Benvenuti | [[Category: Rossolini GM]] | ||
[[Category: Calderone | [[Category: Stoczko M]] | ||
[[Category: Docquier | |||
[[Category: Mangani | |||
[[Category: Rossolini | |||
[[Category: Stoczko | |||
Latest revision as of 12:24, 30 October 2024
New refinement of the crystal structure of BJP-1, a subclass B3 metallo-beta-lactamase of Bradyrhizobium japonicumNew refinement of the crystal structure of BJP-1, a subclass B3 metallo-beta-lactamase of Bradyrhizobium japonicum
Structural highlights
FunctionPublication Abstract from PubMedMetallo-beta-lactamases (MBLs) are important enzymatic factors in resistance to beta-lactam antibiotics that show important structural and functional heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by Bradyrhizobium japonicum that exhibits interesting properties. BJP-1, like CAU-1 of Caulobacter vibrioides, overall poorly recognizes beta-lactam substrates and shows an unusual substrate profile compared to other MBLs. In order to understand the structural basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-A resolution. This revealed significant differences in the conformation and locations of the active-site loops, determining a rather narrow active site and the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds in the active site and represents an obstacle for beta-lactam substrate binding. In order to probe the potential of sulfonamides (known to inhibit various zinc-dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-A resolution), thereby revealing the mode of interaction of these molecules in MBLs. Interestingly, sulfonamide binding resulted in the displacement of the side chain of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the molecule is now found. These data further highlight the structural diversity shown by MBLs but also provide interesting insights in the structure-function relationships of these enzymes. More importantly, we provided the first structural observation of MBL interaction with sulfonamides, which might represent an interesting scaffold for the design of MBL inhibitors. High-resolution crystal structure of the subclass B3 metallo-beta-lactamase BJP-1: rational basis for substrate specificity and interaction with sulfonamides.,Docquier JD, Benvenuti M, Calderone V, Stoczko M, Menciassi N, Rossolini GM, Mangani S Antimicrob Agents Chemother. 2010 Oct;54(10):4343-51. Epub 2010 Aug 9. PMID:20696874[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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