PHLC_CLOPF
ID PHLC_CLOPF Reviewed; 398 AA.
AC Q9RF12;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Phospholipase C;
DE Short=PLC;
DE EC=3.1.4.3;
DE AltName: Full=Alpha-toxin;
DE AltName: Full=Hemolysin;
DE AltName: Full=Lecithinase;
DE AltName: Full=Phosphatidylcholine cholinephosphohydrolase;
DE Flags: Precursor;
GN Name=plc; Synonyms=cpa;
OS Clostridium perfringens.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1502;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, AND X-RAY
RP CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF THE OPEN FORM.
RC STRAIN=SWCP;
RX PubMed=12009886; DOI=10.1021/bi012015v;
RA Justin N., Walker N., Bullifent H.L., Songer G., Bueschel D.M., Jost H.,
RA Naylor C.E., Miller J., Moss D.S., Titball R.W., Basak A.K.;
RT "The first strain of Clostridium perfringens isolated from an avian source
RT has an alpha-toxin with divergent structural and kinetic properties.";
RL Biochemistry 41:6253-6262(2002).
RN [2]
RP REVIEW.
RX PubMed=16887662; DOI=10.1006/anae.1999.0191;
RA Titball R.W., Naylor C.E., Basak A.K.;
RT "The Clostridium perfringens alpha-toxin.";
RL Anaerobe 5:51-64(1999).
RN [3]
RP REVIEW.
RX PubMed=11008117; DOI=10.1016/s1286-4579(00)01281-8;
RA Jepson M., Titball R.W.;
RT "Structure and function of clostridial phospholipases C.";
RL Microbes Infect. 2:1277-1284(2000).
CC -!- FUNCTION: Bacterial hemolysins are exotoxins that attack blood cell
CC membranes and cause cell rupture. Constitutes an essential virulence
CC factor in gas gangrene. Binds to eukaryotic membranes where it
CC hydrolyzes both phosphatidylcholine and sphingomyelin, causing cell
CC rupture. The diacylglycerol produced can activate both the arachidonic
CC acid pathway, leading to modulation of the inflammatory response
CC cascade and thrombosis, and protein kinase C, leading to activation of
CC eukaryotic phospholipases and further membrane damage.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:10604,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:295975; EC=3.1.4.3;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 3 Ca(2+) ions per subunit.;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 3 Zn(2+) ions per subunit.;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DOMAIN: The protein is composed of 2 domains; the N-terminal domain
CC contains the phospholipase C active site (PLC), in a cleft which is
CC also occupied by the 3 zinc ions. The C-terminal domain is a putative
CC phospholipid-recognition domain, which shows structural homology with
CC phospholipid-binding C2-like domains from a range of eukaryotic
CC proteins. The ability to bind membrane phospholipids in a Ca(2+)
CC dependent manner and toxicity is conferred by this C-terminal domain,
CC which also contributes to the sphingomyelinase activity.
CC -!- MISCELLANEOUS: This bacteria was isolated from a diseased swan.
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DR EMBL; AF204209; AAF20094.1; -; Genomic_DNA.
DR PDB; 1KHO; X-ray; 2.40 A; A/B=29-398.
DR PDBsum; 1KHO; -.
DR AlphaFoldDB; Q9RF12; -.
DR SMR; Q9RF12; -.
DR ABCD; Q9RF12; 1 sequenced antibody.
DR EvolutionaryTrace; Q9RF12; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0034480; F:phosphatidylcholine phospholipase C activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR Gene3D; 1.10.575.10; -; 1.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR008947; PLipase_C/P1_nuclease_dom_sf.
DR InterPro; IPR029002; PLPC/GPLD1.
DR InterPro; IPR001531; Zn_PLipaseC.
DR Pfam; PF01477; PLAT; 1.
DR Pfam; PF00882; Zn_dep_PLPC; 1.
DR PRINTS; PR00479; PRPHPHLPASEC.
DR SMART; SM00770; Zn_dep_PLPC; 1.
DR SUPFAM; SSF48537; SSF48537; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS50095; PLAT; 1.
DR PROSITE; PS00384; PROKAR_ZN_DEPEND_PLPC_1; 1.
DR PROSITE; PS51346; PROKAR_ZN_DEPEND_PLPC_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytolysis; Hemolysis; Hydrolase; Metal-binding;
KW Secreted; Signal; Toxin; Virulence; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000250"
FT CHAIN 29..398
FT /note="Phospholipase C"
FT /id="PRO_0000023932"
FT DOMAIN 29..278
FT /note="Zn-dependent PLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00678"
FT DOMAIN 284..398
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 275..283
FT /note="Linker"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 300
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 322
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 38..53
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 60..71
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 73..81
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:1KHO"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 122..138
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 142..159
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 162..165
FT /evidence="ECO:0007829|PDB:1KHO"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 175..185
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 202..208
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 213..234
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 242..272
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 285..292
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 302..310
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 332..338
FT /evidence="ECO:0007829|PDB:1KHO"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 349..357
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 378..384
FT /evidence="ECO:0007829|PDB:1KHO"
FT STRAND 391..396
FT /evidence="ECO:0007829|PDB:1KHO"
SQ SEQUENCE 398 AA; 45598 MW; EF3C95AF603CD5A7 CRC64;
MKRKIYKLLI CATIATSLWA VRTTKVYAWD GKADGTGTHA MIATQGVTIL ENDLSSNEPE
VIRNNLEILK QNMHDLQLGS TYPDYDKNAY DLYQDHFWDP DTDNNFTKDS KWYLSYSIPD
TAESQIRKFS ALARYEWKRG NYKQATFYLG EAMHYFGDAD TPYHAANVTA VDSPGHVKFE
TFAEDRKDQY KINTTGSKTN DAFYSNILTN EDFNSWSKEF ARSFAKTAKD LYYSHANMSC
SWDEWDYAAK VALANSQKGT SGYIYRFLHD VSDGKDSSAN KNVNELVAYI TTGGEKYAGT
DDYMYFGIKT KDGQTQEWTM DNPGNDFMTG SQDTYTFKLK DKNLKIDDIQ NMWIRKSKYT
EFGDDYKPAN IKVIANGNVV LNKDINEWIS GNSTYNIK
