6cd7: Difference between revisions
New page: '''Unreleased structure''' The entry 6cd7 is ON HOLD Authors: Stogios, P.J., Evdokimova, E., Dong, A., Di Leo, R., Savchenko, A., Satchell, K.J., Joachimiak, J., Center for Structural G... |
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==Crystal structure of APH(2")-IVa in complex with plazomicin== | |||
<StructureSection load='6cd7' size='340' side='right'caption='[[6cd7]], [[Resolution|resolution]] 1.53Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6cd7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"streptococcus_casseliflavus"_vaughan_et_al._1979 "streptococcus casseliflavus" vaughan et al. 1979]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6c0c 6c0c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CD7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDS:(2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-{[(2S,3R)-3-amino-6-{[(2-hydroxyethyl)amino]methyl}-3,4-dihydro-2H-pyran-2-yl]oxy}-2-{[3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranosyl]oxy}-3-hydroxycyclohexyl]-2-hydroxybutanamide'>EDS</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aph(2'')-Id ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37734 "Streptococcus casseliflavus" Vaughan et al. 1979])</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=6cd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cd7 OCA], [http://pdbe.org/6cd7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cd7 RCSB], [http://www.ebi.ac.uk/pdbsum/6cd7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cd7 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plazomicin is a next-generation, semisynthetic aminoglycoside antibiotic currently under development for the treatment of infections due to multidrug-resistant Enterobacteriaceae. The compound was designed by chemical modification of the natural product sisomicin to provide protection from common aminoglycoside modifying enzymes that chemically alter these drugs via N-acetylation, O-adenylylation, or O-phosphorylation. In this study, plazomicin was profiled against a panel of isogenic strains of Escherichia coli individually expressing twenty-one aminoglycoside resistance enzymes. Plazomicin retained antibacterial activity against 15 of the 17 modifying enzyme-expressing strains tested. Expression of only two of the modifying enzymes, aac(2')-Ia and aph(2'')-IVa, decreased plazomicin potency. On the other hand, expression of 16S rRNA ribosomal methyltransferases results in a complete lack of plazomicin potency. In vitro enzymatic assessment confirmed that AAC(2')-Ia and APH(2'')-IVa (aminoglycoside acetyltransferase, AAC; aminoglycoside phosphotransferase, APH) were able to utilize plazomicin as a substrate. AAC(2')-Ia and APH(2'')-IVa are limited in their distribution to Providencia stuartii and Enterococci, respectively. These data demonstrate that plazomicin is not modified by a broad spectrum of common aminoglycoside modifying enzymes including those commonly found in Enterobacteriaceae. However, plazomicin is inactive in the presence of 16S rRNA ribosomal methyltransferases, which should be monitored in future surveillance programs. | |||
Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying Enzymes.,Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD ACS Infect Dis. 2018 Apr 19. doi: 10.1021/acsinfecdis.8b00001. PMID:29634241<ref>PMID:29634241</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6cd7" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Streptococcus casseliflavus vaughan et al. 1979]] | |||
[[Category: Large Structures]] | |||
[[Category: Structural genomic]] | |||
[[Category: Dong, A]] | [[Category: Dong, A]] | ||
[[Category: | [[Category: Evdokimova, E]] | ||
[[Category: Joachimiak, J]] | [[Category: Joachimiak, J]] | ||
[[Category: | [[Category: Leo, R Di]] | ||
[[Category: | [[Category: Satchell, K J]] | ||
[[Category: Savchenko, A]] | |||
[[Category: Stogios, P J]] | |||
[[Category: Aminoglycoside]] | |||
[[Category: Aminoglycoside phosphotransferase]] | |||
[[Category: Antibiotic]] | |||
[[Category: Csgid]] | |||
[[Category: Eukaryotic protein kinase-like fold]] | |||
[[Category: Kinase]] | |||
[[Category: Plazomicin]] | |||
[[Category: Transferase]] | |||
[[Category: Transferase-antibiotic complex]] | |||