DEFCO_COPCI
ID DEFCO_COPCI Reviewed; 184 AA.
AC A0A097PTA8;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 25-MAY-2022, entry version 15.
DE RecName: Full=Fungal defensin copsin {ECO:0000303|PubMed:25342741, ECO:0000303|PubMed:28825809};
DE Flags: Precursor;
OS Coprinopsis cinerea (Inky cap fungus) (Hormographiella aspergillata).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Psathyrellaceae; Coprinopsis.
OX NCBI_TaxID=5346;
RN [1] {ECO:0000312|PDB:2MN5}
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, STRUCTURE BY NMR OF
RP 131-186, FUNCTION, DISULFIDE BONDS, PYROGLUTAMATE FORMATION AT GLN-128,
RP SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=AmutBmut;
RX PubMed=25342741; DOI=10.1074/jbc.m114.599878;
RA Essig A., Hofmann D., Munch D., Gayathri S., Kunzler M., Kallio P.T.,
RA Sahl H.G., Wider G., Schneider T., Aebi M.;
RT "Copsin, a novel peptide-based fungal antibiotic interfering with the
RT peptidoglycan synthesis.";
RL J. Biol. Chem. 289:34953-34964(2014).
RN [2]
RP FUNCTION, MUTAGENESIS OF SER-140; THR-143; THR-168 AND THR-173, AND
RP MEMBRANE-BINDING SIMULATION.
RX PubMed=28825809; DOI=10.1021/acs.biochem.7b00697;
RA Franzoi M., van Heuvel Y., Thomann S., Schuerch N., Kallio P.T., Venier P.,
RA Essig A.;
RT "Structural insights into the mode of action of the peptide antibiotic
RT copsin.";
RL Biochemistry 56:4992-5001(2017).
CC -!- FUNCTION: Antimicrobial peptide that acts against Gram-positive
CC bacteria (Listeria spp., Enterococcus spp., B.subtilis, B.anthracis,
CC P.aeruginosa) (PubMed:25342741, PubMed:28825809). Is not active against
CC Gram-negative bacteria (PubMed:25342741). It selectively inhibits
CC peptidoglycan biosynthesis through complex formation with the cell wall
CC precursor lipid II (1:1 molar ratio), probably anchoring lipid II to
CC the membrane, thus inhibiting cell wall synthesis (PubMed:25342741,
CC PubMed:28825809). The interaction with lipid II involves the third
CC position of the pentapeptide (PubMed:25342741). Shows bactericidal
CC activity at about 2-fold minimal inhibitory concentrations (MIC), but
CC does not form pore across the membrane (PubMed:25342741).
CC {ECO:0000269|PubMed:25342741, ECO:0000269|PubMed:28825809}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 1-8. {ECO:0000269|PubMed:25342741};
CC Temperature dependence:
CC Optimum temperature is 4-90 degrees Celsius.
CC {ECO:0000269|PubMed:25342741};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25342741,
CC ECO:0000305|PubMed:28825809}. Target cell membrane
CC {ECO:0000269|PubMed:25342741, ECO:0000305|PubMed:28825809}.
CC Note=specific localization at active cell wall synthesis sites.
CC {ECO:0000269|PubMed:25342741}.
CC -!- PTM: Contains a unique connectivity of 6 cysteine bonds in contrast to
CC most other CS-alpha-beta defensins which are linked by 3 or 4 disulfide
CC bonds. {ECO:0000305}.
CC -!- PTM: Disulfide bonds are essential for structural integrity and
CC antibacterial activity, since activity is lost after treatment with
CC reducing agents. Thanks to disulfide bonds and N-terminal
CC pyroglutamate, the protein is extremely stable in a wide pH and
CC temperature range and insensitive toward proteases.
CC {ECO:0000269|PubMed:25342741}.
CC -!- SIMILARITY: Belongs to the invertebrate defensin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=The antimicrobial peptide database;
CC URL="https://wangapd3.com/database/query_output.php?ID=02440";
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DR EMBL; KM274935; AIU55999.1; -; mRNA.
DR PDB; 2MN5; NMR; -; A=128-184.
DR PDBsum; 2MN5; -.
DR AlphaFoldDB; A0A097PTA8; -.
DR SMR; A0A097PTA8; -.
DR VEuPathDB; FungiDB:CC1G_13813; -.
DR VEuPathDB; FungiDB:CC2G_005004; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR InterPro; IPR041284; Copsin.
DR Pfam; PF18251; Defensin_5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial;
KW Cleavage on pair of basic residues; Defensin; Direct protein sequencing;
KW Disulfide bond; Lipid-binding; Membrane; Pyrrolidone carboxylic acid;
KW Secreted; Signal; Target cell membrane; Target membrane.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..127
FT /evidence="ECO:0000269|PubMed:25342741"
FT /id="PRO_0000449383"
FT CHAIN 128..184
FT /note="Fungal defensin copsin"
FT /id="PRO_5001931724"
FT MOD_RES 128
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:25342741"
FT DISULFID 130..159
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT DISULFID 137..167
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT DISULFID 145..175
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT DISULFID 149..177
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT DISULFID 152..184
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT DISULFID 162..181
FT /evidence="ECO:0000269|PubMed:25342741,
FT ECO:0007744|PDB:2MN5"
FT MUTAGEN 140
FT /note="S->H: Increase in antibacterial activity against
FT both B.subtilis and S.aureus. In k-copsin; important
FT increase in antibacterial activity against both B.subtilis
FT and S.aureus, which is due to a different and stronger
FT interaction with bacterial membranes."
FT /evidence="ECO:0000269|PubMed:28825809"
FT MUTAGEN 143
FT /note="T->H: Increase in antibacterial activity against
FT both B.subtilis and S.aureus. In k-copsin; important
FT increase in antibacterial activity against both B.subtilis
FT and S.aureus, which is due to a different and stronger
FT interaction with bacterial membranes."
FT /evidence="ECO:0000269|PubMed:28825809"
FT MUTAGEN 168
FT /note="T->G: No change in activity against S.aureus, but
FT increase in activity against B.subtilis. In k-copsin;
FT important increase in antibacterial activity against both
FT B.subtilis and S.aureus, which is due to a different and
FT stronger interaction with bacterial membranes."
FT /evidence="ECO:0000269|PubMed:28825809"
FT MUTAGEN 173
FT /note="T->H: No change in activity against S.aureus, but
FT increase in activity against B.subtilis. In k-copsin;
FT important increase in antibacterial activity against both
FT B.subtilis and S.aureus, which is due to a different and
FT stronger interaction with bacterial membranes."
FT /evidence="ECO:0000269|PubMed:28825809"
SQ SEQUENCE 184 AA; 18954 MW; 85CC33494B5AFD75 CRC64;
MKLSTSLLAI VAVASTFIGN ALSATTVPGC FAECIDKAAV AVNCAAGDID CLQASSQFAT
IVSECVATSD CTALSPGSAS DADSINKTFN ILSGLGFIDE ADAFSAADVP EERDLTGLGR
VLPVEKRQNC PTRRGLCVTS GLTACRNHCR SCHRGDVGCV RCSNAQCTGF LGTTCTCINP
CPRC
