PDBsum entry 6tkt

Antitumor protein

PDB id: 6tkt

Contents

Protein chain

93 a.a.

PDB id:

6tkt

Name:

Antitumor protein

Title:

Structure of the bacterial toxin phenomycin

Structure:

Pre-phenomycin. Chain: a. Engineered: yes

Source:

Streptomyces roseoverticillatus. Organism_taxid: 66429. Gene: phm. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

NMR struc:

20 models

Authors:

J.T.Nielsen,F.A.A.Mulder,T.Toerring,T.Poulsen

Key ref:

B.K.Hansen et al. (2020). Structure and Function of the Bacterial Protein Toxin Phenomycin. Structure, 28, 528. PubMed id: 32220302 DOI: 10.1016/j.str.2020.03.003

Date:

28-Nov-19 Release date: 22-Jan-20

Protein chain

Q53805  (Q53805_9ACTN) -  Pre-phenomycin from Streptomyces roseoverticillatus

Seq: 134 a.a.

Struc: 93 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2020.03.003

Structure 28:528 (2020)

PubMed id: 32220302

Structure and Function of the Bacterial Protein Toxin Phenomycin.

B.K.Hansen, C.K.Larsen, J.T.Nielsen, E.B.Svenningsen, L.B.Van, K.M.Jacobsen, M.Bjerring, R.K.Flygaard, L.B.Jenner, L.N.Nejsum, D.E.Brodersen, F.A.A.Mulder, T.Tørring, T.B.Poulsen.

ABSTRACT

Phenomycin is a bacterial mini-protein of 89 amino acids discovered more than 50 years ago with toxicity in the nanomolar regime toward mammalian cells. The protein inhibits the function of the eukaryotic ribosome in cell-free systems and appears to target translation initiation. Several fundamental questions concerning the cellular activity of phenomycin, however, have remained unanswered. In this paper, we have used morphological profiling to show that direct inhibition of translation underlies the toxicity of phenomycin in cells. We have performed studies of the cellular uptake mechanism of phenomycin, showing that endosomal escape is the toxicity-limiting step, and we have solved a solution phase high-resolution structure of the protein using NMR spectroscopy. Through bioinformatic as well as functional comparisons between phenomycin and two homologs, we have identified a peptide segment, which constitutes one of two loops in the structure that is critical for the toxicity of phenomycin.