8xz2: Difference between revisions
m Protected "8xz2" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==The structural model of a homodimeric D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteria== | ||
<StructureSection load='8xz2' size='340' side='right'caption='[[8xz2]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8xz2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XZ2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=8xz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xz2 OCA], [https://pdbe.org/8xz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xz2 RCSB], [https://www.ebi.ac.uk/pdbsum/8xz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xz2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/VANX_ENTFC VANX_ENTFC] Catalyzes hydrolysis of the D-alanyl-D-alanine dipeptide. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacteria that have acquired resistance to most antibiotics, particularly those causing nosocomial infections, create serious problems. Among these, the emergence of vancomycin-resistant enterococci was a tremendous shock, considering that vancomycin is the last resort for controlling methicillin-resistant Staphylococcus aureus. Therefore, there is an urgent need to develop an inhibitor of VanX, a protein involved in vancomycin resistance. Although the crystal structure of VanX has been resolved, its asymmetric unit contains six molecules aligned in a row. We have developed a structural model of VanX as a stable dimer in solution, primarily utilizing nuclear magnetic resonance (NMR) residual dipolar coupling. Despite the 46 kDa molecular mass of the dimer, the analyses, which are typically not as straightforward as those of small proteins around 10 kDa, were successfully conducted. We assigned the main chain using an amino acid-selective unlabeling method. Because we found that the zinc ion-coordinating active sites in the dimer structure were situated in the opposite direction to the dimer interface, we generated an active monomer by replacing an amino acid at the dimer interface. The monomer consists of only 202 amino acids and is expected to be used in future studies to screen and improve inhibitors using NMR. | |||
Analysis of the homodimeric structure of a D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteria.,Konuma T, Takai T, Tsuchiya C, Nishida M, Hashiba M, Yamada Y, Shirai H, Motoda Y, Nagadoi A, Chikaishi E, Akagi KI, Akashi S, Yamazaki T, Akutsu H, Ikegami T Protein Sci. 2024 Jun;33(6):e5002. doi: 10.1002/pro.5002. PMID:38723146<ref>PMID:38723146</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8xz2" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Enterococcus faecium]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Akagi K]] | ||
[[Category: | [[Category: Akashi S]] | ||
[[Category: Nishida | [[Category: Akutsu H]] | ||
[[Category: | [[Category: Chikaishi E]] | ||
[[Category: | [[Category: Hashiba M]] | ||
[[Category: | [[Category: Ikegami T]] | ||
[[Category: | [[Category: Konuma T]] | ||
[[Category: Yamada | [[Category: Motoda Y]] | ||
[[Category: | [[Category: Nagadoi A]] | ||
[[Category: Nishida M]] | |||
[[Category: Oe A]] | |||
[[Category: Shirai H]] | |||
[[Category: Takai T]] | |||
[[Category: Tsuchiya C]] | |||
[[Category: Yamada Y]] | |||
[[Category: Yamazaki T]] | |||
Latest revision as of 11:08, 22 May 2024
The structural model of a homodimeric D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteriaThe structural model of a homodimeric D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteria
Structural highlights
FunctionVANX_ENTFC Catalyzes hydrolysis of the D-alanyl-D-alanine dipeptide. Publication Abstract from PubMedBacteria that have acquired resistance to most antibiotics, particularly those causing nosocomial infections, create serious problems. Among these, the emergence of vancomycin-resistant enterococci was a tremendous shock, considering that vancomycin is the last resort for controlling methicillin-resistant Staphylococcus aureus. Therefore, there is an urgent need to develop an inhibitor of VanX, a protein involved in vancomycin resistance. Although the crystal structure of VanX has been resolved, its asymmetric unit contains six molecules aligned in a row. We have developed a structural model of VanX as a stable dimer in solution, primarily utilizing nuclear magnetic resonance (NMR) residual dipolar coupling. Despite the 46 kDa molecular mass of the dimer, the analyses, which are typically not as straightforward as those of small proteins around 10 kDa, were successfully conducted. We assigned the main chain using an amino acid-selective unlabeling method. Because we found that the zinc ion-coordinating active sites in the dimer structure were situated in the opposite direction to the dimer interface, we generated an active monomer by replacing an amino acid at the dimer interface. The monomer consists of only 202 amino acids and is expected to be used in future studies to screen and improve inhibitors using NMR. Analysis of the homodimeric structure of a D-Ala-D-Ala metallopeptidase, VanX, from vancomycin-resistant bacteria.,Konuma T, Takai T, Tsuchiya C, Nishida M, Hashiba M, Yamada Y, Shirai H, Motoda Y, Nagadoi A, Chikaishi E, Akagi KI, Akashi S, Yamazaki T, Akutsu H, Ikegami T Protein Sci. 2024 Jun;33(6):e5002. doi: 10.1002/pro.5002. PMID:38723146[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||