| Structural highlights
6n60 is a 9 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | rpoA, pez, phs, sez, b3295, JW3257 ("Bacillus coli" Migula 1895), rpoB, groN, nitB, rif, ron, stl, stv, tabD, b3987, JW3950 ("Bacillus coli" Migula 1895), rpoC, tabB, b3988, JW3951 ("Bacillus coli" Migula 1895), rpoZ, b3649, JW3624 ("Bacillus coli" Migula 1895), rpoD ("Bacillus coli" Migula 1895), mcjA ("Bacillus coli" Migula 1895) |
| Activity: | DNA-directed RNA polymerase, with EC number 2.7.7.6 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MCJA_ECOLX] Peptide antibiotic that functions through inhibition of the bacterial DNA-dependent RNA polymerase (RNAP). May inhibit transcription by binding in RNAP secondary channel and blocking nucleotide substrates access to the catalytic center. Exhibits potent bacteriocidal activity against a range of Enterobacteriaceae, including several pathogenic E.coli, Salmonella and Shigella strains. Also acts on the cytoplasmic membrane of Salmonella newport, producing alteration of membrane permeability and disruption of the subsequent gradient dissipation, which inhibits several processes essential for cell viability, such as oxygen consumption. Induces bacterial filamentation in susceptible cells in a non-SOS-dependent way, but this phenotype may result from impaired transcription of genes coding for cell division proteins.[1] [2] [3] [RPOC_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322] [RPOB_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [RPOA_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.[HAMAP-Rule:MF_00059] [RPOZ_ECOLI] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366] [Q0P6L9_ECOLX] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth.[HAMAP-Rule:MF_00963][SAAS:SAAS00535554]
Publication Abstract from PubMed
We report crystal structures of the antibacterial lasso peptides microcin J25 (MccJ25) and capistruin (Cap) bound to their natural enzymatic target, the bacterial RNA polymerase (RNAP). Both peptides bind within the RNAP secondary channel, through which NTP substrates enter the RNAP active site, and sterically block trigger-loop folding, which is essential for efficient catalysis by the RNAP. MccJ25 binds deep within the secondary channel in a manner expected to interfere with NTP substrate binding, explaining the partial competitive mechanism of inhibition with respect to NTPs found previously [Mukhopadhyay J, Sineva E, Knight J, Levy RM, Ebright RH (2004) Mol Cell 14:739-751]. The Cap binding determinant on RNAP overlaps, but is not identical to, that of MccJ25. Cap binds further from the RNAP active site and does not sterically interfere with NTP binding, and we show that Cap inhibition is partially noncompetitive with respect to NTPs. This work lays the groundwork for structure determination of other lasso peptides that target the bacterial RNAP and provides a structural foundation to guide lasso peptide antimicrobial engineering approaches.
Structural mechanism of transcription inhibition by lasso peptides microcin J25 and capistruin.,Braffman NR, Piscotta FJ, Hauver J, Campbell EA, Link AJ, Darst SA Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1273-1278. doi:, 10.1073/pnas.1817352116. Epub 2019 Jan 9. PMID:30626643[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rintoul MR, de Arcuri BF, Salomon RA, Farias RN, Morero RD. The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport. FEMS Microbiol Lett. 2001 Nov 13;204(2):265-70. PMID:11731133
- ↑ Delgado MA, Rintoul MR, Farias RN, Salomon RA. Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25. J Bacteriol. 2001 Aug;183(15):4543-50. PMID:11443089 doi:http://dx.doi.org/10.1128/JB.183.15.4543-4550.2001
- ↑ Yuzenkova J, Delgado M, Nechaev S, Savalia D, Epshtein V, Artsimovitch I, Mooney RA, Landick R, Farias RN, Salomon R, Severinov K. Mutations of bacterial RNA polymerase leading to resistance to microcin j25. J Biol Chem. 2002 Dec 27;277(52):50867-75. Epub 2002 Oct 24. PMID:12401787 doi:http://dx.doi.org/10.1074/jbc.M209425200
- ↑ Braffman NR, Piscotta FJ, Hauver J, Campbell EA, Link AJ, Darst SA. Structural mechanism of transcription inhibition by lasso peptides microcin J25 and capistruin. Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1273-1278. doi:, 10.1073/pnas.1817352116. Epub 2019 Jan 9. PMID:30626643 doi:http://dx.doi.org/10.1073/pnas.1817352116
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