| Structural highlights
5us1 is a 12 chain structure with sequence from "proteus_stuartii"_buttiaux_et_al._1954 "proteus stuartii" buttiaux et al. 1954. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | 8MM, ACO, COA, GOL, TAR |
| Related: | 6c0c |
| Gene: | aac ("Proteus stuartii" Buttiaux et al. 1954) |
| Activity: | Gentamicin 2'-N-acetyltransferase, with EC number 2.3.1.59 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD. Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying Enzymes. ACS Infect Dis. 2018 Apr 19. doi: 10.1021/acsinfecdis.8b00001. PMID:29634241 doi:https://dx.doi.org/10.1021/acsinfecdis.8b00001
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