FemABX Family Members are Novel Nonribosomal Peptidyltransferases and Important Pathogen-specific Drug Targets

Subray Hegde, Thomas E. Shrader

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Pathogen-specific antibiotics kill the offending species without inviting the patient's flora to help develop a resistance mechanism. The current scarcity of pathogen-specific antibiotics reflects the rarity of essential genes that are also not widely represented in and conserved among species. The FemX enzyme that initiates the synthesis of the interchain peptide of the peptidoglycan in a subset of bacterial species was purified from Lactobacillus viridescens. Subsequently, the encoding femX gene was cloned and sequenced using reverse genetics. The femX gene is a member of the femAB family, a large family of genes previously implicated in interchain peptide synthesis but with unknown specific functions. Mutagenesis of the femX gene identified the members of the extended FemABX family as novel non-ribosomal peptidyltransferases. Determinants of FemX complex substrate recognition and a strong stimulator of FemX activity were also identified. The FemABX family members are ideal candidates for pathogen-specific antibiotic development.

Original languageEnglish (US)
Pages (from-to)6998-7003
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number10
DOIs
StatePublished - Mar 9 2001
Externally publishedYes

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Peptidyl Transferases
Pathogens
Genes
Anti-Bacterial Agents
Pharmaceutical Preparations
Reverse Genetics
Mutagenesis
Peptides
Gene encoding
Peptidoglycan
Essential Genes
Lactobacillus
Substrates
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

FemABX Family Members are Novel Nonribosomal Peptidyltransferases and Important Pathogen-specific Drug Targets. / Hegde, Subray; Shrader, Thomas E.

In: Journal of Biological Chemistry, Vol. 276, No. 10, 09.03.2001, p. 6998-7003.

Research output: Contribution to journalArticle

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