Antibacterial lysine analogs that target lysine riboswitches.

Abstract:

:Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine binding to the receptor stabilizes an mRNA tertiary structure that, in most cases, causes transcription termination before the adjacent open reading frame can be expressed. A lysine riboswitch conceivably could be targeted for antibacterial therapy by designing new compounds that bind the riboswitch and suppress lysine biosynthesis and transport genes. As a test of this strategy, we have identified several lysine analogs that bind to riboswitches in vitro and inhibit Bacillus subtilis growth, probably through a mechanism of riboswitch-mediated repression of lysine biosynthesis. These results indicate that riboswitches could serve as new classes of antibacterial drug targets.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Blount KF,Wang JX,Lim J,Sudarsan N,Breaker RR

doi

10.1038/nchembio842

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

44-9

issue

1

eissn

1552-4450

issn

1552-4469

pii

nchembio842

journal_volume

3

pub_type

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