CAP_BURTA
ID CAP_BURTA Reviewed; 47 AA.
AC P0DQM5;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 1.
DT 25-MAY-2022, entry version 3.
DE RecName: Full=Capistruin {ECO:0000303|PubMed:18671394, ECO:0000303|PubMed:20064439, ECO:0000303|PubMed:30626643};
DE Short=Cap {ECO:0000303|PubMed:30626643};
DE AltName: Full=Class II lasso peptide {ECO:0000303|PubMed:18671394, ECO:0000303|PubMed:20064439, ECO:0000303|PubMed:30626643};
DE AltName: Full=Lariat peptide {ECO:0000303|PubMed:20064439, ECO:0000303|PubMed:21396375};
DE AltName: Full=Ribosomally synthesized and post-translationally modified peptide {ECO:0000303|PubMed:21396375, ECO:0000303|PubMed:30626643};
DE Short=RiPP {ECO:0000303|PubMed:21396375, ECO:0000303|PubMed:30626643};
DE Flags: Precursor;
GN Name=CapA {ECO:0000303|PubMed:18671394, ECO:0000303|PubMed:20064439};
GN OrderedLocusNames=BTH_I2437.1 {ECO:0000303|PubMed:16336651};
OS Burkholderia thailandensis (strain ATCC 700388 / DSM 13276 / CIP 106301 /
OS E264).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Burkholderia; pseudomallei group.
OX NCBI_TaxID=271848;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=16336651; DOI=10.1186/1471-2164-6-174;
RA Kim H.S., Schell M.A., Yu Y., Ulrich R.L., Sarria S.H., Nierman W.C.,
RA DeShazer D.;
RT "Bacterial genome adaptation to niches: divergence of the potential
RT virulence genes in three Burkholderia species of different survival
RT strategies.";
RL BMC Genomics 6:174-174(2005).
RN [2]
RP FUNCTION, MASS SPECTROMETRY, STRUCTURE BY NMR OF 29-47, CROSS-LINK, AND
RP EXPRESSION IN E.COLI.
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=18671394; DOI=10.1021/ja802966g;
RA Knappe T.A., Linne U., Zirah S., Rebuffat S., Xie X., Marahiel M.A.;
RT "Isolation and structural characterization of capistruin, a lasso peptide
RT predicted from the genome sequence of Burkholderia thailandensis E264.";
RL J. Am. Chem. Soc. 130:11446-11454(2008).
RN [3]
RP MUTAGENESIS OF ARG-43 AND 43-ARG-PHE-44, AND ALA-SCAN MUTAGENESIS.
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=20064439; DOI=10.1016/j.chembiol.2009.11.009;
RA Knappe T.A., Linne U., Robbel L., Marahiel M.A.;
RT "Insights into the biosynthesis and stability of the lasso peptide
RT capistruin.";
RL Chem. Biol. 16:1290-1298(2009).
RN [4]
RP FUNCTION.
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=21396375; DOI=10.1016/j.jmb.2011.02.060;
RA Kuznedelov K., Semenova E., Knappe T.A., Mukhamedyarov D., Srivastava A.,
RA Chatterjee S., Ebright R.H., Marahiel M.A., Severinov K.;
RT "The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA
RT polymerase.";
RL J. Mol. Biol. 412:842-848(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 29-47 IN COMPLEX WITH E.COLI RNA
RP POLYMERASE, AND FUNCTION.
RX PubMed=30626643; DOI=10.1073/pnas.1817352116;
RA Braffman N.R., Piscotta F.J., Hauver J., Campbell E.A., Link A.J.,
RA Darst S.A.;
RT "Structural mechanism of transcription inhibition by lasso peptides
RT microcin J25 and capistruin.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:1273-1278(2019).
CC -!- FUNCTION: Peptide antibiotic that functions through inhibition of the
CC bacterial DNA-dependent RNA polymerase (RNAP) (PubMed:21396375,
CC PubMed:30626643). Inhibits transcription by binding in RNAP secondary
CC channel, where it sterically blocks the folding of the trigger loop,
CC which is essential for efficient catalysis (PubMed:21396375,
CC PubMed:30626643). In contrast to MccJ25, does not restrict access of
CC nucleotide substrates to the catalytic center and shows a non-
CC competitive mode of inhibition (PubMed:30626643). Shows activity
CC against closely related Gram-negative Burkholderia and Pseudomonas
CC strains (PubMed:18671394). Is not active against Gram-positive bacteria
CC (PubMed:18671394). {ECO:0000269|PubMed:18671394,
CC ECO:0000269|PubMed:21396375, ECO:0000269|PubMed:30626643}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Highly thermostable. {ECO:0000269|PubMed:20064439};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9X2V7,
CC ECO:0000305|PubMed:20064439}.
CC -!- DOMAIN: Is composed of a ring composed by 9 residues, and a tail of 10
CC residues (Probable). The peptide is threaded when the C-terminal tail
CC is inserted throught the isopeptide-bonded ring (Probable).
CC {ECO:0000305|PubMed:18671394}.
CC -!- PTM: It is assumed that the two processing enzymes CapB/CapC convert
CC the precursor protein CapA into the mature lasso peptide capistruin.
CC CapB is assumed to cleave the precursor protein CapA and to set an N-
CC terminal Gly free, whose a-NH2 group acts as the nucleophile in the
CC subsequent cyclization reaction. CapC is most likely involved in the
CC side-chain carboxyl group activation of aspartic acid at position 9
CC generating the electrophile for the condensation reaction. CapD may
CC export capistruin outside of the producing cells.
CC {ECO:0000305|PubMed:20064439}.
CC -!- MASS SPECTROMETRY: Mass=2050; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:18671394};
CC -!- WEB RESOURCE: Name=Biological Magnetic Resonance Data Bank;
CC URL="http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=20014";
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DR EMBL; CP000086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DQM5; -.
DR Proteomes; UP000001930; Chromosome I.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Bacteriocin; Isopeptide bond; Secreted.
FT PROPEP 1..28
FT /evidence="ECO:0000269|PubMed:18671394"
FT /id="PRO_0000450653"
FT PEPTIDE 29..47
FT /note="Capistruin"
FT /evidence="ECO:0000269|PubMed:18671394"
FT /id="PRO_0000450654"
FT SITE 43
FT /note="Basic bulky residue that acts as a plug entrapping
FT the tail within the macrocyclic ring"
FT /evidence="ECO:0000305|PubMed:20064439"
FT CROSSLNK 29..37
FT /note="Isoaspartyl glycine isopeptide (Gly-Asp)"
FT /evidence="ECO:0000269|PubMed:18671394"
FT MUTAGEN 43..44
FT /note="RF->AA: Loss of thermostability. Stays resistance to
FT proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:20064439"
FT MUTAGEN 43
FT /note="R->A: No change in thermostability."
FT /evidence="ECO:0000269|PubMed:20064439"
SQ SEQUENCE 47 AA; 5013 MW; FF7405A2EE3F6679 CRC64;
MVRLLAKLLR STIHGSNGVS LDAVSSTHGT PGFQTPDARV ISRFGFN
