2009
DOI: 10.1128/aac.00275-08
|View full text |Cite
|
Sign up to set email alerts
|

Inhibition of Methionyl-tRNA Synthetase by REP8839 and Effects of Resistance Mutations on Enzyme Activity

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

8
41
0

Year Published

2010
2010
2023
2023

Publication Types

Select...
5
1
1

Relationship

0
7

Authors

Journals

citations
Cited by 45 publications
(49 citation statements)
references
References 45 publications
(51 reference statements)
8
41
0
Order By: Relevance
“…Fewer differences in the inhibitor binding site were observed between trypanosomatid and human mitochondrial MetRS enzymes, with only 5 of 25 residues being different. This also fits with published data that REP8839 inhibits the human mitochondrial enzyme with a K i of 10 nM (12). Of note, REP8839 inhibits the S. aureus MetRS with a K i of 10 pM (12), suggesting that extremely tight binding is possible.…”
Section: Discussionsupporting
confidence: 90%
See 3 more Smart Citations
“…Fewer differences in the inhibitor binding site were observed between trypanosomatid and human mitochondrial MetRS enzymes, with only 5 of 25 residues being different. This also fits with published data that REP8839 inhibits the human mitochondrial enzyme with a K i of 10 nM (12). Of note, REP8839 inhibits the S. aureus MetRS with a K i of 10 pM (12), suggesting that extremely tight binding is possible.…”
Section: Discussionsupporting
confidence: 90%
“…This fits with published data that the diaryl diamine REP8839 (Fig. 6) is essentially inactive on the human cytosolic enzyme, with K i on May 11, 2018 by guest http://aac.asm.org/ being Ͼ20,000 nM (12). Fewer differences in the inhibitor binding site were observed between trypanosomatid and human mitochondrial MetRS enzymes, with only 5 of 25 residues being different.…”
Section: Discussionsupporting
confidence: 90%
See 2 more Smart Citations
“…The challenge for MetRS inhibitors, however, is not biochemical activity but whole-cell activity. The most potent examples at the biochemical level, with IC 50 values in the low nanomolar range, including oxazolone dipeptides and methionyl adenylate isosteres, have shown good selectivity versus human MetRS but lack antibacterial activity in wholecell assays 8 . To date, REP3123 (Figure 1), a novel diaryldiamine, is the only documented selective C. difficile MetRS inhibitor with whole cell activity in a range of clinical C. diffcile isolates 9 .…”
Section: Introductionmentioning
confidence: 99%