DEFPL_PSENR
ID DEFPL_PSENR Reviewed; 95 AA.
AC Q53I06;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Fungal defensin plectasin {ECO:0000303|PubMed:16222292, ECO:0000303|PubMed:19414576, ECO:0000303|PubMed:19472324, ECO:0000303|PubMed:20508130};
DE Flags: Precursor;
GN Name=DEF;
OS Pseudoplectania nigrella (Ebony cup) (Peziza nigrella).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Pezizomycetes;
OC Pezizales; Sarcosomataceae; Pseudoplectania.
OX NCBI_TaxID=96584;
RN [1] {ECO:0000312|PDB:1ZFU}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, STRUCTURE BY
RP NMR OF 56-95, FUNCTION, MASS SPECTROMETRY, AND DISULFIDE BONDS.
RX PubMed=16222292; DOI=10.1038/nature04051;
RA Mygind P.H., Fischer R.L., Schnorr K.M., Hansen M.T., Soenksen C.P.,
RA Ludvigsen S., Raventos D.S., Buskov S., Christensen B., De Maria L.,
RA Taboureau O., Yaver D., Elvig-Joergensen S.G., Soerensen M.V.,
RA Christensen B.E., Kjaerulf S., Frimodt-Moller N., Lehrer R.I., Zasloff M.,
RA Kristensen H.-H.;
RT "Plectasin is a peptide antibiotic with therapeutic potential from a
RT saprophytic fungus.";
RL Nature 437:975-980(2005).
RN [2]
RP PHARMACEUTICAL.
RX PubMed=19414576; DOI=10.1128/aac.01584-08;
RA Andes D., Craig W., Nielsen L.A., Kristensen H.H.;
RT "In vivo pharmacodynamic characterization of a novel plectasin antibiotic,
RT NZ2114, in a murine infection model.";
RL Antimicrob. Agents Chemother. 53:3003-3009(2009).
RN [3]
RP FUNCTION, 3D-STRUCTURE MODELING, MUTAGENESIS OF ASP-67; TYR-84; ALA-86;
RP GLY-88 AND LYS-93, BINDING TO MEMBRANE INTERFACE, AND BINDING TO LIPID II.
RX PubMed=20508130; DOI=10.1126/science.1185723;
RA Schneider T., Kruse T., Wimmer R., Wiedemann I., Sass V., Pag U.,
RA Jansen A., Nielsen A.K., Mygind P.H., Raventos D.S., Neve S., Ravn B.,
RA Bonvin A.M., De Maria L., Andersen A.S., Gammelgaard L.K., Sahl H.G.,
RA Kristensen H.H.;
RT "Plectasin, a fungal defensin, targets the bacterial cell wall precursor
RT Lipid II.";
RL Science 328:1168-1172(2010).
RN [4]
RP FUNCTION.
RX PubMed=25568977; DOI=10.3390/toxins7010034;
RA Xiang F., Xie Z., Feng J., Yang W., Cao Z., Li W., Chen Z., Wu Y.;
RT "Plectasin, first animal toxin-like fungal defensin blocking potassium
RT channels through recognizing channel pore region.";
RL Toxins 7:34-42(2015).
RN [5] {ECO:0000312|PDB:3E7R, ECO:0000312|PDB:3E7U}
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 56-95 OF L- AND D-PLECTASIN,
RP FUNCTION, AND SYNTHESIS OF 56-95.
RX PubMed=19472324; DOI=10.1002/pro.127;
RA Mandal K., Pentelute B.L., Tereshko V., Thammavongsa V., Schneewind O.,
RA Kossiakoff A.A., Kent S.B.;
RT "Racemic crystallography of synthetic protein enantiomers used to determine
RT the X-ray structure of plectasin by direct methods.";
RL Protein Sci. 18:1146-1154(2009).
RN [6] {ECO:0000312|PDB:6K50, ECO:0000312|PDB:6K51}
RP STRUCTURE BY NMR OF 56-95 OF PLECTASIN DERIVATIVE NZ2114, AND MUTAGENESIS
RP OF 64-ASP--GLN-69.
RA Wang J.H., Mao R.Y., Liu X.H.;
RT "Solution structure of plectasin derivative NZ2114.";
RL Submitted (MAY-2019) to the PDB data bank.
CC -!- FUNCTION: Antimicrobial peptide that potently acts against several
CC species of Gram-positive bacteria (PubMed:16222292, PubMed:19472324).
CC It selectively inhibits peptidoglycan biosynthesis through complex
CC formation with the cell wall precursor lipid II (1:1 molar ratio) thus
CC inhibiting cell wall synthesis (PubMed:20508130). It does not disrupt
CC cell membranes (PubMed:20508130). Is especially active against numerous
CC clinical isolates of S.pneumoniae, including all 90 different serotypes
CC and isolates resistant to clinically used antibiotics
CC (PubMed:16222292). In vitro, shows considerable selectivity for
CC bacteria over mammalian cells (PubMed:16222292). The peptide
CC synthesized in D-amino acids does not show antibacterial activity
CC (PubMed:19472324). In vitro, acts on voltage-gated potassium channels
CC by moderately inhibiting mammalian Kv1.3/KCNA3 (IC(50)=2.8 uM), and
CC moderately inhibiting others potassium channels (PubMed:25568977).
CC {ECO:0000269|PubMed:16222292, ECO:0000269|PubMed:25568977}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Host cell membrane
CC {ECO:0000269|PubMed:20508130}.
CC -!- MASS SPECTROMETRY: Mass=4398.8; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:16222292};
CC -!- PHARMACEUTICAL: Plectasin could be used as a possible antibiotic,
CC especially against S.pneumoniae infections.
CC {ECO:0000305|PubMed:16222292}.
CC -!- PHARMACEUTICAL: An improved derivative NZ2114 can be used as an
CC antibiotic for the methicillin-resistant S.aureus (MRSA).
CC {ECO:0000305|PubMed:19414576}.
CC -!- MISCELLANEOUS: In mice infected by S.pneumoniae, it has an efficacy
CC comparable to vancomycin in the peritoneal model and to penicillin in
CC the pneumonia model. {ECO:0000269|PubMed:16222292}.
CC -!- SIMILARITY: Belongs to the invertebrate defensin family. Type 2
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00710}.
CC -!- WEB RESOURCE: Name=The antimicrobial peptide database;
CC URL="https://wangapd3.com/database/query_output.php?ID=00549";
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DR EMBL; AJ964941; CAI83768.1; -; mRNA.
DR PDB; 1ZFU; NMR; -; A=56-95.
DR PDB; 3E7R; X-ray; 1.00 A; L=56-95.
DR PDB; 3E7U; X-ray; 1.35 A; X=56-95.
DR PDB; 6K50; NMR; -; A=56-95.
DR PDB; 6K51; NMR; -; A=56-95.
DR PDBsum; 1ZFU; -.
DR PDBsum; 3E7R; -.
DR PDBsum; 3E7U; -.
DR PDBsum; 6K50; -.
DR PDBsum; 6K51; -.
DR AlphaFoldDB; Q53I06; -.
DR BMRB; Q53I06; -.
DR SMR; Q53I06; -.
DR TCDB; 1.C.47.2.1; the insect/fungal defensin (insect/fungal defensin) family.
DR EvolutionaryTrace; Q53I06; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR CDD; cd00107; Knot1; 1.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR001542; Defensin_invertebrate/fungal.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR Pfam; PF01097; Defensin_2; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51378; INVERT_DEFENSINS; 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; Host cell membrane; Host membrane;
KW Ion channel impairing toxin; Membrane; Pharmaceutical;
KW Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..55
FT /evidence="ECO:0000269|PubMed:16222292"
FT /id="PRO_0000042753"
FT CHAIN 56..95
FT /note="Fungal defensin plectasin"
FT /id="PRO_0000042754"
FT REGION 61..64
FT /note="Binds to membrane interface"
FT /evidence="ECO:0000305|PubMed:20508130"
FT REGION 86..92
FT /note="Binds to membrane interface"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 57
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 58
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 59
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 67
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 73
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 84
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 86
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 88
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 92
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT BINDING 93
FT /ligand="beta-D-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-
FT L-Lys-D-Ala-D-Ala)-di-trans,octa-cis-undecaprenyl
FT diphosphate"
FT /ligand_id="ChEBI:CHEBI:60033"
FT /evidence="ECO:0000305|PubMed:20508130"
FT DISULFID 59..85
FT /evidence="ECO:0000269|PubMed:16222292,
FT ECO:0000269|PubMed:19472324, ECO:0007744|PDB:1ZFU,
FT ECO:0007744|PDB:3E7U"
FT DISULFID 70..92
FT /evidence="ECO:0000269|PubMed:16222292,
FT ECO:0000269|PubMed:19472324, ECO:0007744|PDB:1ZFU,
FT ECO:0007744|PDB:3E7U"
FT DISULFID 74..94
FT /evidence="ECO:0000269|PubMed:16222292,
FT ECO:0000269|PubMed:19472324, ECO:0007744|PDB:1ZFU,
FT ECO:0007744|PDB:3E7U"
FT MUTAGEN 64..69
FT /note="DEDDMQ->NEDDLR: Plectasin derivative NZ2114;
FT increase in antibacterial spectrum by including the
FT methicillin-resistant A.aureus (MRSA)."
FT /evidence="ECO:0000269|PubMed:19414576, ECO:0000305|Ref.6"
FT MUTAGEN 67
FT /note="D->A,C,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y: Complete
FT loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 84
FT /note="Y->A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W: Complete
FT loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 86
FT /note="A->C,D,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y: Complete
FT loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 86
FT /note="A->G: No change of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 88
FT /note="G->A,C,D,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y: Complete
FT loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 93
FT /note="K->A,C,D,E,F,G,H,I,L,M,N,P,Q,S,T,V,W,Y: Complete
FT loss of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT MUTAGEN 93
FT /note="K->R: No change of antibacterial activity."
FT /evidence="ECO:0000269|PubMed:20508130"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:6K51"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1ZFU"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:3E7R"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:3E7R"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:3E7R"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:3E7R"
SQ SEQUENCE 95 AA; 10254 MW; 882903AB610AB018 CRC64;
MQFTTILSIG ITVFGLLNTG AFAAPQPVPE AYAVSDPEAH PDDFAGMDAN QLQKRGFGCN
GPWDEDDMQC HNHCKSIKGY KGGYCAKGGF VCKCY
