Deformylation and protein biosynthesis

Livingston, David M.; Leder, Philip

doi:10.1021/bi00829a059

Cited by 106 publications

(66 citation statements)

References 34 publications

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“…In agreement with this hypothesis, two distinct enzymatic activities could be described: (i) a peptide deformylase capable of cleaving the formyl group from formylmethionine peptides (1,18,28,32) and (ii) a methionine aminopeptidase which removes the N-terminal methionine from methionine peptides (1,18,23,28,32). The gene encoding this methionine aminopeptidase has been identified in Escherichia coli (4).…”

mentioning

confidence: 71%

“…The coupled specificities of the two enzymes therefore explain why alanine, glycine, serine, or valine on the one hand and methionine on the other are usually found as N-terminal amino acids of proteins. However, peptide deformylase could not be further characterized because of its extreme instability (1,18,28 (13). The product of the fint gene plays an essential role for optimal growth of E. coli cells (13), possibly by enabling MetMet tRNAf to participate in the initiation rather than in the elongation step of the translation process (12).…”

mentioning

confidence: 99%

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Evidence that peptide deformylase and methionyl-tRNA(fMet) formyltransferase are encoded within the same operon in Escherichia coli

Meinnel

Blanquet

1993

J Bacteriol

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Overexpression of theftns gene, the first translation unit of a dicistronic operon that also encodes methionyltRNAet formyltransferase in Escherichia col, sustains the overproduction of peptide deformylase activity in crude extracts. This suggests that thefins gene encodes the peptide deformylase. Moreover, thefins gene product has a motif characteristic of metalloproteases, an activity compatible with deformylase. The corresponding protein could be purified to homogeneity. However, its enzymatic activity could not be retained during the purification procedure. As could be expected from the occurrence in its amino acid sequence of a zinc-binding motif characteristic of metallopeptidases, the purified fins product displayed one tightly bound zinc atom.

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mentioning

confidence: 71%

mentioning

confidence: 99%

Evidence that peptide deformylase and methionyl-tRNA(fMet) formyltransferase are encoded within the same operon in Escherichia coli

Meinnel

Blanquet

1993

J Bacteriol

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“…Formyl-methionine-tRNA is necessary for mitochondrial translation initiation (39), and therefore inhibition of HsPDF could decrease the available pool of the aminoacyltRNA necessary for new protein synthesis. However, Livingston and Leder (27) have shown that formyl-methionine-puromycin-tRNA, but not formyl-methionine-tRNA, is a substrate of bacterial deformylase.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Human Peptide Deformylase Disrupts Mitochondrial Function

Escobar-Alvarez

Gardner

Sheth

et al. 2010

Molecular and Cellular Biology

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Deformylases are metalloproteases in bacteria, plants, and humans that remove the N-formyl-methionine off peptides in vitro. The human homolog of peptide deformylase (HsPDF) resides in the mitochondria, along with its putative formylated substrates; however, the cellular function of HsPDF remains elusive. Here we report on the function of HsPDF in mitochondrial translation and oxidative phosphorylation complex biogenesis. Functional HsPDF appears to be necessary for the accumulation of mitochondrial DNA-encoded proteins and assembly of new respiratory complexes containing these proteins. Consequently, inhibition of HsPDF reduces respiratory function and cellular ATP levels, causing dependence on aerobic glycolysis for cell survival. A series of structurally different HsPDF inhibitors and control peptidase inhibitors confirmed that inhibition of HsPDF decreases mtDNA-encoded protein accumulation. Therefore, HsPDF appears to have a role in maintenance of mitochondrial respiratory function, and this function is analogous to that of chloroplast PDF.

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“…The removal of this residue is thought to involve two enzymes; peptide deformylase [3,4] which removes the formyl group and a specific aminopeptidase which removes the methionyl group. Although several groups [4,5,6] have reported methionyl-splitting activity in crude bacterial preparations the nature of this peptidase is still unknown.…”

Section: Introductionmentioning

confidence: 99%