NDB4S_TITST
ID NDB4S_TITST Reviewed; 73 AA.
AC P0DQT1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=Stigmurin {ECO:0000303|PubMed:25805002, ECO:0000303|PubMed:33359395};
DE Flags: Precursor;
OS Tityus stigmurus (Brazilian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX NCBI_TaxID=50344;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, 3D-STRUCTURE MODELING, SYNTHESIS OF
RP 23-39 WITH C-TERMINAL AMIDATION, AND AMIDATION AT LYS-39.
RC TISSUE=Venom gland;
RX PubMed=25805002; DOI=10.1016/j.peptides.2015.03.003;
RA de Melo E.T., Estrela A.B., Santos E.C., Machado P.R., Farias K.J.,
RA Torres T.M., Carvalho E., Lima J.P., Silva-Junior A.A., Barbosa E.G.,
RA Fernandes-Pedrosa M.F.;
RT "Structural characterization of a novel peptide with antimicrobial activity
RT from the venom gland of the scorpion Tityus stigmurus: stigmurin.";
RL Peptides 68:3-10(2015).
RN [2]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, BIOASSAY IN ANIMAL MODEL OF
RP SEPSIS, AND SYNTHESIS OF 23-39 WITH C-TERMINAL AMIDATION.
RX PubMed=27567704; DOI=10.1016/j.toxicon.2016.08.016;
RA Daniele-Silva A., Machado R.J., Monteiro N.K., Estrela A.B., Santos E.C.,
RA Carvalho E., Araujo Junior R.F., Melo-Silveira R.F., Rocha H.A.,
RA Silva-Junior A.A., Fernandes-Pedrosa M.F.;
RT "Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: assessment of
RT structure and therapeutic potential in experimental sepsis.";
RL Toxicon 121:10-21(2016).
RN [3]
RP FUNCTION, MUTAGENESIS OF SER-25; SER-29 AND GLY-32, AND SYNTHESIS OF 23-39
RP WITH C-TERMINAL AMIDATION.
RX PubMed=29670004; DOI=10.3390/toxins10040161;
RA Parente A.M.S., Daniele-Silva A., Furtado A.A., Melo M.A., Lacerda A.F.,
RA Queiroz M., Moreno C., Santos E., Rocha H.A.O., Barbosa E.G., Carvalho E.,
RA Silva-Junior A.A., Silva M.S., Fernandes-Pedrosa M.F.;
RT "Analogs of the scorpion venom peptide stigmurin: structural assessment,
RT toxicity, and increased antimicrobial activity.";
RL Toxins 10:0-0(2018).
RN [4]
RP FUNCTION, MUTAGENESIS OF SER-25; SER-29; GLY-32; GLY-33 AND SER-36,
RP SYNTHESIS OF 23-39 WITH C-TERMINAL AMIDATION, AND 3D-STRUCTURE MODELING.
RX PubMed=30709056; DOI=10.3390/ijms20030623;
RA Amorim-Carmo B., Daniele-Silva A., Parente A.M.S., Furtado A.A.,
RA Carvalho E., Oliveira J.W.F., Santos E.C.G., Silva M.S., Silva S.R.B.,
RA Silva-Junior A.A., Monteiro N.K., Fernandes-Pedrosa M.F.;
RT "Potent and broad-spectrum antimicrobial activity of analogs from the
RT scorpion peptide stigmurin.";
RL Int. J. Mol. Sci. 20:0-0(2019).
RN [5]
RP STRUCTURE BY NMR OF 23-39, FUNCTION, BIOASSAY, AND SYNTHESIS OF 23-39 WITH
RP C-TERMINAL AMIDATION.
RX PubMed=33359395; DOI=10.1016/j.peptides.2020.170478;
RA Daniele-Silva A., Rodrigues S.C.S., Dos Santos E.C.G., Queiroz Neto M.F.,
RA Rocha H.A.O., Silva-Junior A.A.D., Resende J.M., Araujo R.M.,
RA Fernandes-Pedrosa M.F.;
RT "NMR three-dimensional structure of the cationic peptide Stigmurin from
RT Tityus stigmurus scorpion venom: in vitro antioxidant and in vivo
RT antibacterial and healing activity.";
RL Peptides 137:170478-170478(2021).
CC -!- FUNCTION: Antimicrobial peptide with activity against Gram-positive
CC bacterial strains (S.aureus (MIC=2-140 uM), methicillin-resistant
CC S.aureus (MRSA) (MIC=8-17 uM), S.epidermidis (MIC=1.17 uM), and the
CC yeasts C.albicans, C.krusei, and C.glabrata (MIC=34-69 uM))
CC (PubMed:25805002, PubMed:27567704, PubMed:29670004, PubMed:30709056).
CC Acts by disrupting the cell membrane (observed on outer layer of the
CC S.aureus) (PubMed:30709056). Is not active against Gram-negative
CC bacteria (E.coli, E.Cloacae, P.aeruginosa), and the Gram-positive
CC bacterium E.faecalis (PubMed:25805002, PubMed:27567704,
CC PubMed:29670004, PubMed:30709056). Also shows toxicity against several
CC cell lines, but possess low hemolytic activity at the highest
CC concentration tested (PubMed:25805002, PubMed:29670004,
CC PubMed:30709056). Also shows antiparasitic activity against Trypanosoma
CC cruzi by decreasing the viability of the epimastigote and
CC trypomastigote forms of the parasite (PubMed:29670004,
CC PubMed:30709056). Displays high hydroxyl radical scavenging activity
CC (antioxidant action) (PubMed:33359395). In a wound infection model, the
CC topical application of this peptide demonstrates antibacterial effects,
CC as well as an ability to accelerate wound closure speed, which suggests
CC the induction of tissue repair (PubMed:33359395). In the model of
CC polymicrobial sepsis, it exhibits an antibiotic effect, reducing the
CC levels of microorganisms in the infectious focus and the inflammatory
CC responses in the lung and cecum of septic animals (PubMed:27567704).
CC {ECO:0000269|PubMed:25805002, ECO:0000269|PubMed:27567704,
CC ECO:0000269|PubMed:29670004, ECO:0000269|PubMed:30709056,
CC ECO:0000269|PubMed:33359395}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Stable to pH variation. {ECO:0000269|PubMed:27567704};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:25805002}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25805002}.
CC -!- SIMILARITY: Belongs to the non-disulfide-bridged peptide (NDBP)
CC superfamily. Short antimicrobial peptide (group 4) family.
CC {ECO:0000305}.
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DR EMBL; JK483709; -; NOT_ANNOTATED_CDS; mRNA.
DR PDB; 6VL2; NMR; -; A=23-39.
DR PDBsum; 6VL2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Antibiotic; Antimicrobial; Fungicide; Secreted;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000305|PubMed:25805002"
FT PEPTIDE 23..39
FT /note="Stigmurin"
FT /evidence="ECO:0000305|PubMed:25805002"
FT /id="PRO_0000454781"
FT PROPEP 45..73
FT /evidence="ECO:0000305|PubMed:25805002"
FT /id="PRO_0000454782"
FT MOD_RES 39
FT /note="Lysine amide"
FT /evidence="ECO:0000305|PubMed:25805002"
FT MUTAGEN 25
FT /note="S->K: In StigA16; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity."
FT /evidence="ECO:0000269|PubMed:29670004"
FT MUTAGEN 25
FT /note="S->K: StigA31; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity."
FT /evidence="ECO:0000269|PubMed:30709056"
FT MUTAGEN 29
FT /note="S->K: In StigA6; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity. In
FT StigA16; Gain of antibacterial activity towards Gram-
FT negative bacteria, and towards the Gram-positive
FT E.faecalis, increase in activity towards fungal strains,
FT and increase in antiparasitic activity. StigA31; Gain of
FT antibacterial activity towards Gram-negative bacteria, and
FT towards the Gram-positive E.faecalis, increase in activity
FT towards fungal strains, and increase in antiparasitic
FT activity."
FT /evidence="ECO:0000269|PubMed:29670004,
FT ECO:0000269|PubMed:30709056"
FT MUTAGEN 32..33
FT /note="GG->KK: StigA25; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity. StigA31;
FT Gain of antibacterial activity towards Gram-negative
FT bacteria, and towards the Gram-positive E.faecalis,
FT increase in activity towards fungal strains, and increase
FT in antiparasitic activity."
FT /evidence="ECO:0000269|PubMed:30709056"
FT MUTAGEN 32
FT /note="G->K: In StigA6; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity. In
FT StigA16; Gain of antibacterial activity towards Gram-
FT negative bacteria, and towards the Gram-positive
FT E.faecalis, increase in activity towards fungal strains,
FT and increase in antiparasitic activity."
FT /evidence="ECO:0000269|PubMed:29670004"
FT MUTAGEN 36
FT /note="S->K: StigA25; Gain of antibacterial activity
FT towards Gram-negative bacteria, and towards the Gram-
FT positive E.faecalis, increase in activity towards fungal
FT strains, and increase in antiparasitic activity. StigA31;
FT Gain of antibacterial activity towards Gram-negative
FT bacteria, and towards the Gram-positive E.faecalis,
FT increase in activity towards fungal strains, and increase
FT in antiparasitic activity."
FT /evidence="ECO:0000269|PubMed:30709056"
SQ SEQUENCE 73 AA; 8469 MW; 0B963EC02514D3E9 CRC64;
MQIKHLITLF FLVLIVADQC SAFFSLIPSL VGGLISAFKG RRKREISAQI EQYKDLQKRE
AELEKLLDRL PMY
