7bzi: Difference between revisions
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The | ==The mutant variant of PNGM-1. H91 was substituted for alanine to study metal coordination.== | ||
<StructureSection load='7bzi' size='340' side='right'caption='[[7bzi]], [[Resolution|resolution]] 1.94Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7bzi]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultured_bacterium Uncultured bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BZI 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]] 1.94Å</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=7bzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bzi OCA], [https://pdbe.org/7bzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bzi RCSB], [https://www.ebi.ac.uk/pdbsum/7bzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bzi ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A2U8UYM6_9BACT A0A2U8UYM6_9BACT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The increasing incidence of community- and hospital-acquired infections with multidrug-resistant (MDR) bacteria poses a critical threat to public health and the healthcare system. Although beta-lactam antibiotics are effective against most bacterial infections, some bacteria are resistant to beta-lactam antibiotics by producing beta-lactamases. Among beta-lactamases, metallo-beta-lactamases (MBLs) are especially worrisome as only a few inhibitors have been developed against them. In MBLs, the metal ions play an important role as they coordinate a catalytic water molecule that hydrolyzes beta-lactam rings. We determined the crystal structures of different variants of PNGM-1, an ancient MBL with additional tRNase Z activity. The variants were generated by site-directed mutagenesis targeting metal-coordinating residues. In PNGM-1, both zinc ions are coordinated by six coordination partners in an octahedral geometry, and the zinc-centered octahedrons share a common face. Structures of the PNGM-1 variants confirm that the substitution of a metal-coordinating residue causes the loss of metal binding and beta-lactamase activity. Compared with PNGM-1, subclass B3 MBLs lack one metal-coordinating residue, leading to a shift in the metal-coordination geometry from an octahedral to tetrahedral geometry. Our results imply that a subtle change in the metal-binding site of MBLs can markedly change their metal-coordination geometry and catalytic activity. | |||
Structural Study of Metal Binding and Coordination in Ancient Metallo-beta-Lactamase PNGM-1 Variants.,Park YS, Kim TY, Park H, Lee JH, Nguyen DQ, Hong MK, Lee SH, Kang LW Int J Mol Sci. 2020 Jul 12;21(14). pii: ijms21144926. doi: 10.3390/ijms21144926. PMID:32664695<ref>PMID:32664695</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7bzi" style="background-color:#fffaf0;"></div> | ||
[[Category: Kang | |||
[[Category: Park | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Uncultured bacterium]] | |||
[[Category: Kang LW]] | |||
[[Category: Lee JH]] | |||
[[Category: Park YS]] | |||
Latest revision as of 18:44, 29 November 2023
The mutant variant of PNGM-1. H91 was substituted for alanine to study metal coordination.The mutant variant of PNGM-1. H91 was substituted for alanine to study metal coordination.
Structural highlights
FunctionPublication Abstract from PubMedThe increasing incidence of community- and hospital-acquired infections with multidrug-resistant (MDR) bacteria poses a critical threat to public health and the healthcare system. Although beta-lactam antibiotics are effective against most bacterial infections, some bacteria are resistant to beta-lactam antibiotics by producing beta-lactamases. Among beta-lactamases, metallo-beta-lactamases (MBLs) are especially worrisome as only a few inhibitors have been developed against them. In MBLs, the metal ions play an important role as they coordinate a catalytic water molecule that hydrolyzes beta-lactam rings. We determined the crystal structures of different variants of PNGM-1, an ancient MBL with additional tRNase Z activity. The variants were generated by site-directed mutagenesis targeting metal-coordinating residues. In PNGM-1, both zinc ions are coordinated by six coordination partners in an octahedral geometry, and the zinc-centered octahedrons share a common face. Structures of the PNGM-1 variants confirm that the substitution of a metal-coordinating residue causes the loss of metal binding and beta-lactamase activity. Compared with PNGM-1, subclass B3 MBLs lack one metal-coordinating residue, leading to a shift in the metal-coordination geometry from an octahedral to tetrahedral geometry. Our results imply that a subtle change in the metal-binding site of MBLs can markedly change their metal-coordination geometry and catalytic activity. Structural Study of Metal Binding and Coordination in Ancient Metallo-beta-Lactamase PNGM-1 Variants.,Park YS, Kim TY, Park H, Lee JH, Nguyen DQ, Hong MK, Lee SH, Kang LW Int J Mol Sci. 2020 Jul 12;21(14). pii: ijms21144926. doi: 10.3390/ijms21144926. PMID:32664695[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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