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Botulinum neurotoxin type D (BoNT/D) (EC 3.4.24.69) (Bontoxilysin-D) [Cleaved into: Botulinum neurotoxin D light chain; Botulinum neurotoxin D heavy chain]

 BXD_CBDP                Reviewed;        1276 AA.
P19321;
01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
01-NOV-1990, sequence version 1.
05-DEC-2018, entry version 162.
RecName: Full=Botulinum neurotoxin type D;
Short=BoNT/D;
AltName: Full=Bontoxilysin-D;
Contains:
RecName: Full=Botulinum neurotoxin D light chain;
Short=LC;
EC=3.4.24.69 {ECO:0000269|PubMed:8175689};
Contains:
RecName: Full=Botulinum neurotoxin D heavy chain;
Short=HC;
Flags: Precursor;
Name=botD;
Clostridium botulinum D phage (Clostridium botulinum D bacteriophage).
Viruses; dsDNA viruses, no RNA stage; Caudovirales; Myoviridae.
NCBI_TaxID=29342;
NCBI_TaxID=1491; Clostridium botulinum.
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=BVD/-3 / Type D;
PubMed=2216736; DOI=10.1093/nar/18.18.5556;
Binz T., Kurazono H., Popoff M.R., Eklund M.W., Sakaguchi G.,
Kozaki S., Krieglstein K., Henschen A., Gill D.M., Niemann H.;
"Nucleotide sequence of the gene encoding Clostridium botulinum
neurotoxin type D.";
Nucleic Acids Res. 18:5556-5556(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=CB-16 / Type D / phage d-16 phi;
PubMed=1420572; DOI=10.1292/jvms.54.905;
Sunagawa H., Ohyama T., Watanabe T., Inoue K.;
"The complete amino acid sequence of the Clostridium botulinum type D
neurotoxin, deduced by nucleotide sequence analysis of the encoding
phage d-16 phi genome.";
J. Vet. Med. Sci. 54:905-913(1992).
[3]
PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN
TYPE D), AND RELEASED AS SINGLE CHAIN.
STRAIN=D-1873 / Type D, and South African / Type D;
PubMed=2668193;
Moriishi K., Syuto B., Kubo S., Oguma K.;
"Molecular diversity of neurotoxins from Clostridium botulinum type D
strains.";
Infect. Immun. 57:2886-2891(1989).
[4]
PROTEIN SEQUENCE OF 2-21 AND 443-462, RELEASED AS DICHAIN, SUBUNIT,
AND SUBCELLULAR LOCATION.
STRAIN=CB-16 / Type D / phage d-16 phi;
PubMed=8569530; DOI=10.1111/j.1348-0421.1995.tb02229.x;
Ohyama T., Watanabe T., Fujinaga Y., Inoue K., Sunagawa H., Fujii N.,
Oguma K.;
"Characterization of nontoxic-nonhemagglutinin component of the two
types of progenitor toxin (M and L) produced by Clostridium botulinum
type D CB-16.";
Microbiol. Immunol. 39:457-465(1995).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-11 AND
443-456, RELEASED AS SINGLE CHAIN, SUBUNIT, AND SUBCELLULAR LOCATION.
STRAIN=D-4947 / Type D;
PubMed=11713244; DOI=10.1074/jbc.M106762200;
Kouguchi H., Watanabe T., Sagane Y., Sunagawa H., Ohyama T.;
"In vitro reconstitution of the Clostridium botulinum type D
progenitor toxin.";
J. Biol. Chem. 277:2650-2656(2002).
[6]
PROTEIN SEQUENCE OF 2-6, RELEASED AS SINGLE CHAIN, SUBUNIT, AND
SUBCELLULAR LOCATION.
STRAIN=D-4947 / Type D;
PubMed=17581814; DOI=10.1074/jbc.M703446200;
Hasegawa K., Watanabe T., Suzuki T., Yamano A., Oikawa T., Sato Y.,
Kouguchi H., Yoneyama T., Niwa K., Ikeda T., Ohyama T.;
"A novel subunit structure of Clostridium botulinum serotype D toxin
complex with three extended arms.";
J. Biol. Chem. 282:24777-24783(2007).
[7]
FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D LIGHT
CHAIN), IDENTIFICATION OF SUBSTRATE, CATALYTIC ACTIVITY, ACTIVITY
REGULATION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), AND SUBCELLULAR
LOCATION (BOTULINUM NEUROTOXIN D LIGHT CHAIN).
STRAIN=D-1873 / Type D;
PubMed=8175689;
Yamasaki S., Baumeister A., Binz T., Blasi J., Link E., Cornille F.,
Roques B., Fykse E.M., Suedhof T.C., Jahn R., Niemann H.;
"Cleavage of members of the synaptobrevin/VAMP family by types D and F
botulinal neurotoxins and tetanus toxin.";
J. Biol. Chem. 269:12764-12772(1994).
[8]
FUNCTION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), AND CATALYTIC ACTIVITY.
STRAIN=Type D;
PubMed=8197120; DOI=10.1073/pnas.91.11.4688;
Yamasaki S., Hu Y., Binz T., Kalkuhl A., Kurazono H., Tamura T.,
Jahn R., Kandel E., Niemann H.;
"Synaptobrevin/vesicle-associated membrane protein (VAMP) of Aplysia
californica: structure and proteolysis by tetanus toxin and botulinal
neurotoxins type D and F.";
Proc. Natl. Acad. Sci. U.S.A. 91:4688-4692(1994).
[9]
SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), RELEASED AS
SINGLE CHAIN, AND BIOTECHNOLOGY.
STRAIN=Type D;
PubMed=15584922; DOI=10.1111/j.1471-4159.2004.02844.x;
Bade S., Rummel A., Reisinger C., Karnath T., Ahnert-Hilger G.,
Bigalke H., Binz T.;
"Botulinum neurotoxin type D enables cytosolic delivery of
enzymatically active cargo proteins to neurones via unfolded
translocation intermediates.";
J. Neurochem. 91:1461-1472(2004).
[10]
FUNCTION (BOTULINUM NEUROTOXIN TYPE D), RELEASED AS DICHAIN,
EUKARYOTIC TARGET RANGE, SUBUNIT, AND SUBCELLULAR LOCATION.
STRAIN=D-1873 / Type D;
PubMed=16252491; DOI=10.1637/7347-022305R1.1;
Takeda M., Tsukamoto K., Kohda T., Matsui M., Mukamoto M., Kozaki S.;
"Characterization of the neurotoxin produced by isolates associated
with avian botulism.";
Avian Dis. 49:376-381(2005).
[11]
FUNCTION (BOTULINUM NEUROTOXIN D HEAVY CHAIN), POSSIBLE LACK OF
PROTEINACEOUS RECEPTOR, DOMAIN, AND LIPID-BINDING.
STRAIN=D-1873 / Type D;
PubMed=16115873; DOI=10.1074/jbc.M507596200;
Tsukamoto K., Kohda T., Mukamoto M., Takeuchi K., Ihara H., Saito M.,
Kozaki S.;
"Binding of Clostridium botulinum type C and D neurotoxins to
ganglioside and phospholipid. Novel insights into the receptor for
clostridial neurotoxins.";
J. Biol. Chem. 280:35164-35171(2005).
[12]
DISCUSSION OF BELT FUNCTION, AND DOMAIN.
PubMed=17907800; DOI=10.1371/journal.ppat.0030113;
Brunger A.T., Breidenbach M.A., Jin R., Fischer A., Santos J.S.,
Montal M.;
"Botulinum neurotoxin heavy chain belt as an intramolecular chaperone
for the light chain.";
PLoS Pathog. 3:1191-1194(2007).
[13]
EUKARYOTIC TARGET RANGE.
PubMed=17913314; DOI=10.1016/j.vaccine.2007.08.051;
Steinman A., Galon N., Arazi A., Bar-Giora Y., Shpigel N.Y.;
"Cattle immune response to botulinum type D toxoid: results of a
vaccination study.";
Vaccine 25:7636-7640(2007).
[14]
FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY
CHAIN).
PubMed=19650874; DOI=10.1111/j.1471-4159.2009.06298.x;
Rummel A., Haefner K., Mahrhold S., Darashchonak N., Holt M., Jahn R.,
Beermann S., Karnath T., Bigalke H., Binz T.;
"Botulinum neurotoxins C, E and F bind gangliosides via a conserved
binding site prior to stimulation-dependent uptake with botulinum
neurotoxin F utilising the three isoforms of SV2 as second receptor.";
J. Neurochem. 110:1942-1954(2009).
[15]
FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY
CHAIN), POSSIBLE PROTEIN RECEPTOR, INTERACTION WITH EUKARYOTIC SV2B,
AND SUBCELLULAR LOCATION.
STRAIN=BVD/-3 / Type D;
PubMed=21483489; DOI=10.1371/journal.ppat.1002008;
Peng L., Tepp W.H., Johnson E.A., Dong M.;
"Botulinum neurotoxin D uses synaptic vesicle protein SV2 and
gangliosides as receptors.";
PLoS Pathog. 7:E1002008-E1002008(2011).
[16]
FUNCTION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), SUBSTRATE SPECIFICITY,
AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=22289120; DOI=10.1111/j.1348-0421.2012.00434.x;
Yamamoto H., Ida T., Tsutsuki H., Mori M., Matsumoto T., Kohda T.,
Mukamoto M., Goshima N., Kozaki S., Ihara H.;
"Specificity of botulinum protease for human VAMP family proteins.";
Microbiol. Immunol. 56:245-253(2012).
[17]
BIOTECHNOLOGY.
PubMed=24029240; DOI=10.1210/en.2013-1427;
Somm E., Bonnet N., Zizzari P., Tolle V., Toulotte A., Jones R.,
Epelbaum J., Martinez A., Hueppi P.S., Aubert M.L.;
"Comparative inhibition of the GH/IGF-I axis obtained with either the
targeted secretion inhibitor SXN101959 or the somatostatin analog
octreotide in growing male rats.";
Endocrinology 154:4237-4248(2013).
[18]
REVIEW.
PubMed=28356439; DOI=10.1124/pr.116.012658;
Pirazzini M., Rossetto O., Eleopra R., Montecucco C.;
"Botulinum neurotoxins: Biology, pharmacology, and toxicology.";
Pharmacol. Rev. 69:200-235(2017).
[19] {ECO:0000244|PDB:2FPQ}
X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1-436 IN COMPLEX WITH ZINC,
AND COFACTOR.
STRAIN=D-1873 / Type D / phage d-16 phi;
PubMed=16519520; DOI=10.1021/bi052518r;
Arndt J.W., Chai Q., Christian T., Stevens R.C.;
"Structure of botulinum neurotoxin type D light chain at 1.65 A
resolution: repercussions for VAMP-2 substrate specificity.";
Biochemistry 45:3255-3262(2006).
[20] {ECO:0000244|PDB:3N7J}
X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 862-1276, AND DOMAIN.
STRAIN=D-1873 / Type D / phage d-16 phi;
PubMed=20731382; DOI=10.1021/bi100865f;
Karalewitz A.P., Kroken A.R., Fu Z., Baldwin M.R., Kim J.J.,
Barbieri J.T.;
"Identification of a unique ganglioside binding loop within botulinum
neurotoxins C and D-SA.";
Biochemistry 49:8117-8126(2010).
[21] {ECO:0000244|PDB:3OBR, ECO:0000244|PDB:3OBT}
X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 863-1276 IN COMPLEX WITH
N-ACETYLNEURAMINIC ACID, FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND
BOTULINUM NEUROTOXIN D HEAVY CHAIN), DOMAIN, GANGLIOSIDE-BINDING, AND
MUTAGENESIS OF LYS-1192; ASP-1233; TYR-1235; TRP-1238; ARG-1239;
PHE-1240; PHE-1242; ASN-1244; TYR-1246; VAL-1251; ASN-1253; LYS-1257
AND SER-1262.
STRAIN=BVD/-3 / Type D;
PubMed=20704566; DOI=10.1042/BJ20101042;
Strotmeier J., Lee K., Volker A.K., Mahrhold S., Zong Y., Zeiser J.,
Zhou J., Pich A., Bigalke H., Binz T., Rummel A., Jin R.;
"Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-
binding sites in a ganglioside-dependent manner.";
Biochem. J. 431:207-216(2010).
[22] {ECO:0000244|PDB:3RMX, ECO:0000244|PDB:3RMY}
X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTATED 862-1276, FUNCTION
(BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY CHAIN),
SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN D HEAVY CHAIN),
GANGLIOSIDE-BINDING, AND MUTAGENESIS OF TRP-1238; ARG-1239 AND
PHE-1240.
STRAIN=D-1873 / Type D;
PubMed=21632541; DOI=10.1074/jbc.M111.254086;
Kroken A.R., Karalewitz A.P., Fu Z., Kim J.J., Barbieri J.T.;
"Novel ganglioside-mediated entry of botulinum neurotoxin serotype D
into neurons.";
J. Biol. Chem. 286:26828-26837(2011).
[23] {ECO:0000244|PDB:5BQM, ECO:0000244|PDB:5BQN}
X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-896 IN COMPLEX WITH ZINC,
COFACTOR, DOMAIN, BIOTECHNOLOGY, AND DISULFIDE BOND.
PubMed=26324071; DOI=10.1038/srep13397;
Masuyer G., Davies J.R., Moore K., Chaddock J.A., Ravi Acharya K.;
"Structural analysis of Clostridium botulinum neurotoxin type D as a
platform for the development of targeted secretion inhibitors.";
Sci. Rep. 5:13397-13397(2015).
-!- FUNCTION: Botulinum neurotoxin type D: Botulinum toxin causes
flaccid paralysis by inhibiting neurotransmitter (acetylcholine)
release from the presynaptic membranes of nerve terminals of the
eukaryotic host skeletal and autonomic nervous system, with
frequent heart or respiratory failure (PubMed:8175689,
PubMed:16252491). Precursor of botulinum neurotoxin D for which a
proteinaceous coreceptor is controversial. In double SV2A/SV2B
knockout mice this toxin does not degrade its synaptobrevin
target; introducing SV2A, SV2B or SV2C restores target cleavage
(PubMed:21483489). Recognition of SV2 by this toxin does not occur
via SV2 glycosylation or its large extracellular loop 4
(PubMed:21483489). Another group does not find a convincing
interaction with SV2 (PubMed:21632541). Thus a protein receptor
for this BoNT serotype has yet to be definitively proven.
Recognizes at least 1 complex polysialylated ganglioside found on
neural tissue. Electrical stimulation increases uptake of toxin in
an ex vivo assay, presumably by transiently exposing a receptor
usually found in eukaryotic target synaptic vesicles
(PubMed:19650874, PubMed:21483489, PubMed:21632541). Upon synaptic
vesicle recycling the toxin is taken up via the endocytic pathway;
when the pH of the toxin-containing endosome drops a structural
rearrangement occurs so that the N-terminus of the heavy chain
(HC) forms pores that allows the light chain (LC) to translocate
into the cytosol (By similarity). Once in the cytosol the
disulfide bond linking the 2 subunits is reduced and LC cleaves
its target protein on synaptic vesicles, preventing their fusion
with the cytoplasmic membrane and thus neurotransmitter release
(By similarity). Requires complex eukaryotic host
polysialogangliosides for full neurotoxicity and for binding to
neurons (PubMed:20704566, PubMed:21483489).
{ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:16252491,
ECO:0000269|PubMed:19650874, ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541,
ECO:0000269|PubMed:8175689, ECO:0000305}.
-!- FUNCTION: Botulinum neurotoxin D light chain: Has proteolytic
activity (PubMed:8175689, PubMed:8197120). After translocation
into the eukaryotic host cytosol, inhibits neurotransmitter
release by acting as a zinc endopeptidase that cleaves the '61-
Lys-|-Leu-62' bond of synaptobrevin-1 (VAMP1), and the equivalent
'Lys-|-Leu' sites in VAMP2 and VAMP3 (PubMed:8175689). Cleaves the
'49-Lys-|-Ile-50' bond of A.californica synaptobrevin (AC P35589)
(PubMed:8197120). This chain probably has to be partially unfolded
to translocate into the eukaryotic host cell cytosol
(PubMed:15584922). {ECO:0000269|PubMed:8175689,
ECO:0000269|PubMed:8197120, ECO:0000305|PubMed:15584922}.
-!- FUNCTION: Botulinum neurotoxin D heavy chain: Responsible for host
epithelial cell transcytosis, host nerve cell targeting and
translocation of light chain (LC) into eukaryotic host cell
cytosol. Composed of 3 subdomains; the translocation domain (TD),
and N-terminus and C-terminus of the receptor-binding domain
(RBD). The RBD is responsible for the adherence of the toxin to
the eukaryotic target cell surface. The N-terminus of the TD wraps
an extended belt around the perimeter of the LC, protecting Zn(2+)
in the active site; it may also prevent premature LC dissociation
from the translocation channel and protect toxin prior to
translocation (PubMed:17907800). The TD inserts into synaptic
vesicle membrane to allow translocation into the host cytosol (By
similarity). The RBD binds eukaryotic host
phosphatidylethanolamine, which may serve as toxin receptor
(PubMed:16115873). Treatment of synaptosomes with proteinase K
does not reduce HC binding, suggesting there is no protein
receptor or it is protected from extracellular proteases
(PubMed:16115873). HC significantly decreases uptake and toxicity
of whole BoNT/D (PubMed:19650874, PubMed:21483489). HC also
interferes with uptake of tetanus toxin (PubMed:19650874). Has 2
closely located carbohydrate-binding receptor sites and binds at
least 1 GT1b ganglioside (PubMed:20704566). Bind gangliosides in
the order GD2 > GT1b > GD1b (PubMed:21632541). Interacts with
eukaryotic target protein SV2B (synaptic vesicle glycoprotein 2B)
(PubMed:21483489). Expression of SV2A, SV2B or SV2C in mice
knocked-out for the SV2 proteins restores entry of BoNT/D and
cleavage of VAMP2, suggesting SV2 acts as its receptor
(PubMed:21483489). Unlike BoNT/A and BoNT/E, toxin uptake is not
mediated by large extracellular loop 4 of SV2 (PubMed:21483489).
Another group finds very poor interaction with SV2 proteins,
suggesting the possible protein receptor may not have been
identified (PubMed:21632541). {ECO:0000250|UniProtKB:P0DPI0,
ECO:0000269|PubMed:16115873, ECO:0000269|PubMed:19650874,
ECO:0000269|PubMed:20704566, ECO:0000269|PubMed:21483489,
ECO:0000269|PubMed:21632541, ECO:0000305|PubMed:17907800}.
-!- CATALYTIC ACTIVITY:
Reaction=Limited hydrolysis of proteins of the neuroexocytosis
apparatus, synaptobrevins, SNAP25 or syntaxin. No detected
action on small molecule substrates.; EC=3.4.24.69;
Evidence={ECO:0000269|PubMed:8175689,
ECO:0000269|PubMed:8197120};
-!- COFACTOR:
Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
Evidence={ECO:0000269|PubMed:16519520,
ECO:0000269|PubMed:26324071};
Note=Binds 1 zinc ion per subunit (PubMed:16519520,
PubMed:26324071). {ECO:0000269|PubMed:16519520,
ECO:0000269|PubMed:26324071};
-!- ACTIVITY REGULATION: Botulinum neurotoxin D light chain: Inhibited
by dipicolinic acid, captopril, 1,10-phenanthroline and EDTA.
{ECO:0000269|PubMed:8175689}.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=28.9 uM for over-expressed human VAMP1
{ECO:0000269|PubMed:22289120};
KM=28.0 uM for over-expressed human VAMP2
{ECO:0000269|PubMed:22289120};
KM=11.1 uM for over-expressed human VAMP3
{ECO:0000269|PubMed:22289120};
Note=kcat is 0.59, 146.60 and 113.41 s(-1) for over-expressed
human VAMP1, VAMP2 and VAMP3 respectively.
{ECO:0000269|PubMed:22289120};
-!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light
chain (LC) and a heavy chain (HC) (PubMed:26324071). The LC has
the proteolytic/pharmacological activity (PubMed:8175689,
PubMed:8197120). The N- and C-termini of the HC mediate channel
formation and eukaryotic host cell binding, respectively. Can also
be purified in complex with a non-toxic component that is larger
than the HC (PubMed:16252491). Single chain toxin from strain D-
4947 copurifies with NTHNA, and in complexes that include NTNHA,
HA-70, HA-33 and HA-17 (PubMed:11713244, PubMed:17581814). Dichain
toxin from strain CB-16 phage d-16 phi copurifies with NTHNA, and
in complexes that include NTNHA, HA-55, HA-33, HA-22 and HA-17
(PubMed:8569530). The stoichiometry of the whole complex has been
modeled as one BoNT/D, one NTNHA, three HA-70, six HA-33 and three
HA-17 (PubMed:17581814). HC interacts with eukaryotic protein
synaptic vesicle glycoprotein 2B (SV2B), which may serve as its
receptor (PubMed:21483489). Another group does not find a
convincing interaction with SV2 (PubMed:21632541).
{ECO:0000269|PubMed:11713244, ECO:0000269|PubMed:16252491,
ECO:0000269|PubMed:16519520, ECO:0000269|PubMed:17581814,
ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541,
ECO:0000269|PubMed:8175689, ECO:0000269|PubMed:8197120,
ECO:0000269|PubMed:8569530, ECO:0000305|PubMed:26324071}.
-!- SUBCELLULAR LOCATION: Botulinum neurotoxin type D: Secreted
{ECO:0000269|PubMed:11713244, ECO:0000269|PubMed:17581814,
ECO:0000269|PubMed:2668193}.
-!- SUBCELLULAR LOCATION: Botulinum neurotoxin D light chain: Secreted
{ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}. Note=In
animals that have ingested BoNT/D LC acts in the eukaryotic host
cytosol (Probable). {ECO:0000305|PubMed:15584922,
ECO:0000305|PubMed:8175689}.
-!- SUBCELLULAR LOCATION: Botulinum neurotoxin D heavy chain: Secreted
{ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}.
Note=Upon incubation with hippocampal cell colocalizes with SV2C,
probably in host synaptic vesicles (PubMed:21483489). Upon
incubation with primary neurons HC colocalizes with synaptophysin
probably in synaptic vesicles of presynaptic cells; a small
portion also colocalizes with RAB5 and may be in synaptic vesicle
protein sorting endosomes (PubMed:21632541). Probably integrates
into the eukaryotic host synaptic vesicle membrane.
{ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541,
ECO:0000305}.
-!- DOMAIN: Botulinum neurotoxin D light chain: Has protease activity
(PubMed:8175689, PubMed:8197120). {ECO:0000269|PubMed:8175689,
ECO:0000269|PubMed:8197120}.
-!- DOMAIN: Botulinum neurotoxin D heavy chain: Has 3 functional
domains; the translocation domain (TD) and the receptor-binding
domain (RBD) which is further subdivided into N- and C-terminal
domains (N-RBD and C-RBD, also called Hcn and Hcc)
(PubMed:20731382, PubMed:20704566). The N-terminus of the TD wraps
an extended belt around the perimeter of the LC which occludes the
catalytic pocket (PubMed:26324071). The belt region may be a
pseudosubstrate inhibitor which serves as an intramolecular
chaperone for the LC prior to its translocation into the host
cytosol (PubMed:17907800). {ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:20731382, ECO:0000269|PubMed:26324071,
ECO:0000305|PubMed:17907800}.
-!- BIOTECHNOLOGY: Cargo proteins fused to the N-terminus of whole
toxin are imported into neurons; stabilized cargo proteins are
poorer substrates, suggesting partial unfolding of the cargo
protein is necessary for import (PubMed:15584922).
{ECO:0000269|PubMed:15584922}.
-!- BIOTECHNOLOGY: Can be used for targeted secretion inhibition in
eukaryotic cells. A construct with a mammalian growth hormone-
releasing factor ligand domain (GHRH) inserted between the LC and
TD, when injected into rats, leads to decreased growth hormone
production. The GHRH ligand domain binds to the GHRH receptor on
somatotrophs where it is taken up into endosomes. There the TD
inserts into the membrane, releasing LC which cleaves
synaptobrevin and inhibits growth hormone exocytosis
(PubMed:24029240, PubMed:26324071). {ECO:0000269|PubMed:24029240,
ECO:0000305|PubMed:26324071}.
-!- MISCELLANEOUS: There are seven antigenically distinct forms of
botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes
are quite frequent. Types C and D can undergo domain swapping to
create hybrid types.
-!- MISCELLANEOUS: Botulism poisoning is usually food-borne, either by
ingesting toxin or bacterial-contaminated food, or less frequently
by inhalation poisoning. In both cases the neurotoxin binds to the
apical surface of epithelial cells in the gut or airway. Toxin
undergoes receptor-mediated endocytosis (using a different
receptor than on target nerve cells), transcytosis across the
epithelial cells and release into the general circulation. Once in
the general circulation it binds to its target cells.
{ECO:0000250|UniProtKB:P0DPI0}.
-!- MISCELLANEOUS: Botulinum type D neurotoxin is synthesized by D
strains of C.botulinum which carry the appropriate bacteriophage.
{ECO:0000305|PubMed:1420572, ECO:0000305|PubMed:20731382,
ECO:0000305|PubMed:2216736}.
-!- MISCELLANEOUS: Botulinum type D South African (D-SA) neurotoxin is
released from bacteria as a single chain and presumably cleaved by
host proteases into the active dichain (PubMed:2668193). Botulinum
type D-1873 neurotoxin is released from bacteria as an already-
cleaved dichain (PubMed:16252491). Toxin from strain CB-16 phage
d-16 phi is released as an alread-cleaved dichain
(PubMed:8569530). Another toxin (possibly from phage CE-beta) is
released from over-producing E.coli as a single chain
(PubMed:15584922). Type D-4947 is released as a single chain
(PubMed:17581814). {ECO:0000269|PubMed:15584922,
ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:17581814,
ECO:0000269|PubMed:2668193, ECO:0000269|PubMed:8569530}.
-!- MISCELLANEOUS: This protein can also be encoded on a prophage.
{ECO:0000305}.
-!- MISCELLANEOUS: BoNT/D causes animal botulism; it is 1,000-fold
less toxic in chickens than BoNT/C1 (PubMed:16252491,
PubMed:16115873). Cattle botulism is often caused by type D
(PubMed:17913314). {ECO:0000269|PubMed:16252491,
ECO:0000269|PubMed:17913314, ECO:0000305|PubMed:16115873}.
-!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
-!- CAUTION: The existence of a proteinaceous coreceptor is unclear.
In double SV2A/SV2B knockout mice this toxin does not degrade its
VAMP target; introducing SV2A, SV2B or SV2C restores target
cleavage (PubMed:21483489). However another group does not find a
convincing interaction with SV2 (PubMed:21632541).
{ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541}.
-!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
Neurotoxins;
URL="https://botdb.abcc.ncifcrf.gov/";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; X54254; CAA38175.1; -; Genomic_DNA.
EMBL; S49407; AAB24244.1; -; Genomic_DNA.
PIR; S11455; S11455.
PDB; 2FPQ; X-ray; 1.65 A; A=1-436.
PDB; 3N7J; X-ray; 2.00 A; A=862-1276.
PDB; 3OBR; X-ray; 1.72 A; A=863-1276.
PDB; 3OBT; X-ray; 2.00 A; A=863-1276.
PDB; 3OGG; X-ray; 1.65 A; A=863-1276.
PDB; 3RMX; X-ray; 2.75 A; A/B/C/D=862-1276.
PDB; 3RMY; X-ray; 2.30 A; A/B/C/D=862-1276.
PDB; 5BQM; X-ray; 3.10 A; A/C=1-437, B/D=450-861.
PDB; 5BQN; X-ray; 2.30 A; A=1-437, A=450-862.
PDBsum; 2FPQ; -.
PDBsum; 3N7J; -.
PDBsum; 3OBR; -.
PDBsum; 3OBT; -.
PDBsum; 3OGG; -.
PDBsum; 3RMX; -.
PDBsum; 3RMY; -.
PDBsum; 5BQM; -.
PDBsum; 5BQN; -.
ProteinModelPortal; P19321; -.
SMR; P19321; -.
UniLectin; P19321; -.
PRIDE; P19321; -.
BRENDA; 3.4.24.69; 1462.
Reactome; R-HSA-5250955; Toxicity of botulinum toxin type D (BoNT/D).
EvolutionaryTrace; P19321; -.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:1905576; F:ganglioside GT1b binding; IDA:UniProtKB.
GO; GO:0004222; F:metalloendopeptidase activity; EXP:Reactome.
GO; GO:0008320; F:protein transmembrane transporter activity; TAS:Reactome.
GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:InterPro.
Gene3D; 1.20.1120.10; -; 1.
InterPro; IPR000395; Bot/tetX_LC.
InterPro; IPR036248; Clostridium_toxin_transloc.
InterPro; IPR013320; ConA-like_dom_sf.
InterPro; IPR011065; Kunitz_inhibitor_STI-like_sf.
InterPro; IPR013104; Toxin_rcpt-bd_C.
InterPro; IPR012928; Toxin_rcpt-bd_N.
InterPro; IPR012500; Toxin_trans.
Pfam; PF01742; Peptidase_M27; 1.
Pfam; PF07951; Toxin_R_bind_C; 1.
Pfam; PF07953; Toxin_R_bind_N; 1.
Pfam; PF07952; Toxin_trans; 1.
PRINTS; PR00760; BONTOXILYSIN.
SUPFAM; SSF49899; SSF49899; 1.
SUPFAM; SSF50386; SSF50386; 1.
SUPFAM; SSF58091; SSF58091; 1.
PROSITE; PS00142; ZINC_PROTEASE; 1.
1: Evidence at protein level;
3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
Lipid-binding; Metal-binding; Metalloprotease; Neurotoxin; Protease;
Secreted; Toxin; Virulence; Zinc.
INIT_MET 1 1 Removed. {ECO:0000269|PubMed:11713244,
ECO:0000269|PubMed:17581814,
ECO:0000269|PubMed:8569530}.
CHAIN 2 1276 Botulinum neurotoxin type D.
/FTId=PRO_0000444906.
CHAIN 2 442 Botulinum neurotoxin D light chain.
/FTId=PRO_0000029219.
CHAIN 443 1276 Botulinum neurotoxin D heavy chain.
{ECO:0000269|PubMed:8569530,
ECO:0000305|PubMed:11713244}.
/FTId=PRO_0000029220.
REGION 443 862 Translocation domain (TD).
{ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:20731382}.
REGION 458 547 Belt. {ECO:0000269|PubMed:26324071}.
REGION 863 1082 N-terminus of receptor binding domain (N-
RBD), Hcn. {ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:20731382}.
REGION 1083 1276 C-terminus of receptor binding domain (C-
RBD), Hcc. {ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:20731382}.
REGION 1172 1173 N-acetyl-beta-neuraminic acid.
{ECO:0000244|PDB:3OBT,
ECO:0000269|PubMed:20704566}.
REGION 1235 1245 Ganglioside-binding loop.
{ECO:0000269|PubMed:21632541}.
MOTIF 1252 1255 Host ganglioside-binding motif.
{ECO:0000250|UniProtKB:P0DPI0,
ECO:0000305|PubMed:20704566}.
ACT_SITE 230 230 {ECO:0000255|PROSITE-ProRule:PRU10095}.
METAL 229 229 Zinc; via tele nitrogen; catalytic.
{ECO:0000244|PDB:2FPQ,
ECO:0000244|PDB:5BQM,
ECO:0000269|PubMed:16519520,
ECO:0000269|PubMed:26324071}.
METAL 233 233 Zinc; via tele nitrogen; catalytic.
{ECO:0000244|PDB:2FPQ,
ECO:0000244|PDB:5BQM,
ECO:0000269|PubMed:16519520,
ECO:0000269|PubMed:26324071}.
METAL 269 269 Zinc; catalytic. {ECO:0000244|PDB:2FPQ,
ECO:0000244|PDB:5BQM,
ECO:0000269|PubMed:16519520,
ECO:0000269|PubMed:26324071}.
BINDING 1192 1192 N-acetyl-beta-neuraminic acid.
{ECO:0000244|PDB:3OBT,
ECO:0000269|PubMed:20704566}.
BINDING 1239 1239 N-acetyl-beta-neuraminic acid.
{ECO:0000244|PDB:3OBT,
ECO:0000269|PubMed:20704566}.
DISULFID 437 450 Interchain (between light and heavy
chains). {ECO:0000244|PDB:5BQM,
ECO:0000244|PDB:5BQN,
ECO:0000305|PubMed:26324071}.
VARIANT 15 16 ND -> PV (in strain: D-SA).
VARIANT 17 18 ND -> LQ (in strain: D-1873).
VARIANT 452 452 K -> Q (in strain: D-SA and D-4947).
VARIANT 457 457 R -> F (in strain: D-1873).
VARIANT 457 457 R -> T (in strain: D-SA).
VARIANT 462 462 A -> D (in strain: D-1873).
VARIANT 489 489 K -> N (in strain: CB16).
VARIANT 644 644 N -> K (in strain: CB16).
VARIANT 1122 1122 Q -> R (in strain: CB16).
MUTAGEN 1192 1192 K->A: Decreased binding of heavy chain
(HC) to synaptosomes. Significantly
decreased HC binding, whole toxin is
dramatically less neurotoxic; when
associated with A-1239.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1233 1233 D->A: Significantly decreased binding of
heavy chain (HC) to synaptosomes, whole
toxin is significantly less neurotoxic.
Dramatically decreased HC binding, whole
toxin is dramatically less neurotoxic;
when associated with A-1239.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1235 1235 Y->A: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is significantly less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1235 1235 Y->W: Increased binding of heavy chain to
synaptosomes, whole toxin has half
neurotoxicity.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1238 1238 W->A: Dramatically decreased binding of
heavy chain (HC) to synaptosomes, whole
toxin is dramatically less neurotoxic.
Loss of HC binding to GD1b, GT1b, GD2 and
synaptic vesicles, ganglioside-binding
loop is disordered in crystal.
{ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:21632541}.
MUTAGEN 1238 1238 W->F,Y: Decreased binding of heavy chain
to synaptosomes, whole toxin is
significantly less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1238 1238 W->L: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is dramatically less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1239 1239 R->A: Significantly decreased binding of
heavy chain (HC) to synaptosomes, whole
toxin is dramatically less neurotoxic.
Dramatically decreased HC binding, whole
toxin is dramatically less neurotoxic;
when associated with A-1192.
Significantly decreased HC binding, whole
toxin is dramatically less neurotoxic;
when associated with A-1233. Decrease in
HC binding to GD1b, GT1b, GD2 and
synaptic vesicles.
{ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:21632541}.
MUTAGEN 1239 1239 R->Y: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is dramatically less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1240 1240 F->A: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is dramatically less neurotoxic.
Significant decrease in HC binding to
GD1b, GT1b, GD2 and synaptic vesicles,
GBL is well ordered in crystal.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1240 1240 F->W: Increased binding of heavy chain
(HC) to synaptosomes, whole toxin is
slightly less neurotoxic. Slightly
greater than wild-type HC binding to
GT1b. {ECO:0000269|PubMed:20704566,
ECO:0000269|PubMed:21632541}.
MUTAGEN 1242 1242 F->S: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is dramatically less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1242 1242 F->W: No effect on heavy chain binding to
synaptosomes, whole toxin is slightly
less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1244 1244 N->A: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is significantly less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1246 1246 Y->A,S,W: Significantly decreased binding
of heavy chain to synaptosomes, whole
toxin is significantly less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1251 1251 V->F: Significantly decreased binding of
heavy chain to synaptosomes, whole toxin
is significantly less neurotoxic.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1253 1253 N->A: Significantly decreased binding of
heavy chain to synaptosomes.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1257 1257 K->A: Decreased binding of heavy chain to
synaptosomes.
{ECO:0000269|PubMed:20704566}.
MUTAGEN 1262 1262 S->F: Decreased binding of heavy chain to
synaptosomes.
{ECO:0000269|PubMed:20704566}.
STRAND 16 23 {ECO:0000244|PDB:2FPQ}.
STRAND 34 40 {ECO:0000244|PDB:2FPQ}.
STRAND 43 46 {ECO:0000244|PDB:2FPQ}.
STRAND 53 55 {ECO:0000244|PDB:5BQM}.
TURN 67 69 {ECO:0000244|PDB:2FPQ}.
TURN 74 77 {ECO:0000244|PDB:2FPQ}.
HELIX 80 97 {ECO:0000244|PDB:2FPQ}.
HELIX 101 112 {ECO:0000244|PDB:2FPQ}.
STRAND 120 122 {ECO:0000244|PDB:5BQM}.
STRAND 126 128 {ECO:0000244|PDB:2FPQ}.
TURN 132 134 {ECO:0000244|PDB:2FPQ}.
STRAND 136 142 {ECO:0000244|PDB:2FPQ}.
STRAND 145 152 {ECO:0000244|PDB:2FPQ}.
STRAND 155 159 {ECO:0000244|PDB:2FPQ}.
HELIX 169 172 {ECO:0000244|PDB:5BQM}.
HELIX 181 183 {ECO:0000244|PDB:2FPQ}.
STRAND 184 186 {ECO:0000244|PDB:2FPQ}.
STRAND 190 193 {ECO:0000244|PDB:2FPQ}.
STRAND 201 203 {ECO:0000244|PDB:2FPQ}.
TURN 212 214 {ECO:0000244|PDB:5BQM}.
STRAND 218 220 {ECO:0000244|PDB:2FPQ}.
HELIX 223 238 {ECO:0000244|PDB:2FPQ}.
STRAND 247 249 {ECO:0000244|PDB:5BQM}.
HELIX 267 273 {ECO:0000244|PDB:2FPQ}.
HELIX 275 280 {ECO:0000244|PDB:2FPQ}.
HELIX 283 306 {ECO:0000244|PDB:2FPQ}.
STRAND 309 312 {ECO:0000244|PDB:2FPQ}.
HELIX 313 318 {ECO:0000244|PDB:2FPQ}.
HELIX 319 329 {ECO:0000244|PDB:2FPQ}.
HELIX 344 355 {ECO:0000244|PDB:2FPQ}.
HELIX 360 366 {ECO:0000244|PDB:2FPQ}.
STRAND 380 384 {ECO:0000244|PDB:5BQM}.
TURN 390 392 {ECO:0000244|PDB:2FPQ}.
TURN 395 397 {ECO:0000244|PDB:2FPQ}.
HELIX 403 405 {ECO:0000244|PDB:2FPQ}.
STRAND 408 410 {ECO:0000244|PDB:5BQM}.
HELIX 411 413 {ECO:0000244|PDB:2FPQ}.
TURN 415 417 {ECO:0000244|PDB:2FPQ}.
STRAND 421 423 {ECO:0000244|PDB:2FPQ}.
TURN 426 428 {ECO:0000244|PDB:5BQN}.
STRAND 433 437 {ECO:0000244|PDB:5BQM}.
STRAND 451 454 {ECO:0000244|PDB:5BQN}.
TURN 464 466 {ECO:0000244|PDB:5BQM}.
HELIX 470 472 {ECO:0000244|PDB:5BQM}.
STRAND 493 500 {ECO:0000244|PDB:5BQN}.
STRAND 515 518 {ECO:0000244|PDB:5BQN}.
STRAND 525 527 {ECO:0000244|PDB:5BQN}.
STRAND 533 536 {ECO:0000244|PDB:5BQM}.
STRAND 537 540 {ECO:0000244|PDB:5BQN}.
HELIX 542 549 {ECO:0000244|PDB:5BQM}.
HELIX 551 558 {ECO:0000244|PDB:5BQN}.
HELIX 560 564 {ECO:0000244|PDB:5BQN}.
HELIX 569 576 {ECO:0000244|PDB:5BQN}.
HELIX 579 587 {ECO:0000244|PDB:5BQM}.
STRAND 590 592 {ECO:0000244|PDB:5BQN}.
TURN 596 598 {ECO:0000244|PDB:5BQN}.
STRAND 600 606 {ECO:0000244|PDB:5BQN}.
STRAND 609 611 {ECO:0000244|PDB:5BQN}.
STRAND 615 619 {ECO:0000244|PDB:5BQN}.
STRAND 622 624 {ECO:0000244|PDB:5BQN}.
HELIX 628 632 {ECO:0000244|PDB:5BQM}.
TURN 638 641 {ECO:0000244|PDB:5BQM}.
HELIX 643 647 {ECO:0000244|PDB:5BQN}.
HELIX 652 655 {ECO:0000244|PDB:5BQM}.
STRAND 669 671 {ECO:0000244|PDB:5BQN}.
HELIX 680 682 {ECO:0000244|PDB:5BQN}.
HELIX 688 707 {ECO:0000244|PDB:5BQN}.
HELIX 731 734 {ECO:0000244|PDB:5BQN}.
HELIX 738 745 {ECO:0000244|PDB:5BQN}.
HELIX 747 752 {ECO:0000244|PDB:5BQN}.
HELIX 754 774 {ECO:0000244|PDB:5BQN}.
HELIX 792 801 {ECO:0000244|PDB:5BQN}.
HELIX 814 818 {ECO:0000244|PDB:5BQN}.
HELIX 830 836 {ECO:0000244|PDB:5BQN}.
HELIX 854 857 {ECO:0000244|PDB:5BQN}.
HELIX 864 867 {ECO:0000244|PDB:3OGG}.
STRAND 868 875 {ECO:0000244|PDB:3OGG}.
STRAND 878 881 {ECO:0000244|PDB:3OGG}.
STRAND 883 885 {ECO:0000244|PDB:3OGG}.
STRAND 888 891 {ECO:0000244|PDB:3OGG}.
STRAND 896 901 {ECO:0000244|PDB:3OGG}.
STRAND 904 907 {ECO:0000244|PDB:3OGG}.
STRAND 909 911 {ECO:0000244|PDB:3OBT}.
STRAND 914 917 {ECO:0000244|PDB:3OGG}.
HELIX 919 921 {ECO:0000244|PDB:5BQN}.
STRAND 931 939 {ECO:0000244|PDB:3OGG}.
HELIX 941 944 {ECO:0000244|PDB:3OGG}.
STRAND 948 954 {ECO:0000244|PDB:3OGG}.
STRAND 957 959 {ECO:0000244|PDB:3OGG}.
STRAND 961 967 {ECO:0000244|PDB:3OGG}.
STRAND 970 976 {ECO:0000244|PDB:3OGG}.
STRAND 982 988 {ECO:0000244|PDB:3OGG}.
TURN 991 993 {ECO:0000244|PDB:3OGG}.
STRAND 1003 1009 {ECO:0000244|PDB:3OGG}.
STRAND 1013 1019 {ECO:0000244|PDB:3OGG}.
STRAND 1022 1028 {ECO:0000244|PDB:3OGG}.
HELIX 1030 1034 {ECO:0000244|PDB:5BQN}.
HELIX 1036 1038 {ECO:0000244|PDB:5BQN}.
STRAND 1040 1044 {ECO:0000244|PDB:3OGG}.
HELIX 1046 1049 {ECO:0000244|PDB:5BQN}.
HELIX 1051 1054 {ECO:0000244|PDB:5BQN}.
STRAND 1055 1065 {ECO:0000244|PDB:3OGG}.
HELIX 1069 1079 {ECO:0000244|PDB:3OGG}.
TURN 1080 1083 {ECO:0000244|PDB:3OGG}.
STRAND 1090 1092 {ECO:0000244|PDB:3OGG}.
STRAND 1098 1103 {ECO:0000244|PDB:3OGG}.
STRAND 1109 1114 {ECO:0000244|PDB:3OGG}.
STRAND 1117 1122 {ECO:0000244|PDB:3OGG}.
STRAND 1135 1139 {ECO:0000244|PDB:3OGG}.
STRAND 1150 1152 {ECO:0000244|PDB:3RMX}.
STRAND 1154 1161 {ECO:0000244|PDB:3OGG}.
STRAND 1164 1170 {ECO:0000244|PDB:3OGG}.
STRAND 1188 1196 {ECO:0000244|PDB:3OGG}.
HELIX 1201 1203 {ECO:0000244|PDB:3OGG}.
STRAND 1204 1209 {ECO:0000244|PDB:3OGG}.
STRAND 1218 1222 {ECO:0000244|PDB:3OGG}.
STRAND 1224 1226 {ECO:0000244|PDB:3OGG}.
STRAND 1228 1235 {ECO:0000244|PDB:3OGG}.
TURN 1239 1242 {ECO:0000244|PDB:3RMY}.
STRAND 1245 1253 {ECO:0000244|PDB:3OGG}.
HELIX 1255 1257 {ECO:0000244|PDB:3OGG}.
HELIX 1261 1263 {ECO:0000244|PDB:3OGG}.
STRAND 1265 1268 {ECO:0000244|PDB:3OGG}.
SEQUENCE 1276 AA; 146872 MW; C1EC50F46C8233E2 CRC64;
MTWPVKDFNY SDPVNDNDIL YLRIPQNKLI TTPVKAFMIT QNIWVIPERF SSDTNPSLSK
PPRPTSKYQS YYDPSYLSTD EQKDTFLKGI IKLFKRINER DIGKKLINYL VVGSPFMGDS
STPEDTFDFT RHTTNIAVEK FENGSWKVTN IITPSVLIFG PLPNILDYTA SLTLQGQQSN
PSFEGFGTLS ILKVAPEFLL TFSDVTSNQS SAVLGKSIFC MDPVIALMHE LTHSLHQLYG
INIPSDKRIR PQVSEGFFSQ DGPNVQFEEL YTFGGLDVEI IPQIERSQLR EKALGHYKDI
AKRLNNINKT IPSSWISNID KYKKIFSEKY NFDKDNTGNF VVNIDKFNSL YSDLTNVMSE
VVYSSQYNVK NRTHYFSRHY LPVFANILDD NIYTIRDGFN LTNKGFNIEN SGQNIERNPA
LQKLSSESVV DLFTKVCLRL TKNSRDDSTC IKVKNNRLPY VADKDSISQE IFENKIITDE
TNVQNYSDKF SLDESILDGQ VPINPEIVDP LLPNVNMEPL NLPGEEIVFY DDITKYVDYL
NSYYYLESQK LSNNVENITL TTSVEEALGY SNKIYTFLPS LAEKVNKGVQ AGLFLNWANE
VVEDFTTNIM KKDTLDKISD VSVIIPYIGP ALNIGNSALR GNFNQAFATA GVAFLLEGFP
EFTIPALGVF TFYSSIQERE KIIKTIENCL EQRVKRWKDS YQWMVSNWLS RITTQFNHIN
YQMYDSLSYQ ADAIKAKIDL EYKKYSGSDK ENIKSQVENL KNSLDVKISE AMNNINKFIR
ECSVTYLFKN MLPKVIDELN KFDLRTKTEL INLIDSHNII LVGEVDRLKA KVNESFENTM
PFNIFSYTNN SLLKDIINEY FNSINDSKIL SLQNKKNALV DTSGYNAEVR VGDNVQLNTI
YTNDFKLSSS GDKIIVNLNN NILYSAIYEN SSVSFWIKIS KDLTNSHNEY TIINSIEQNS
GWKLCIRNGN IEWILQDVNR KYKSLIFDYS ESLSHTGYTN KWFFVTITNN IMGYMKLYIN
GELKQSQKIE DLDEVKLDKT IVFGIDENID ENQMLWIRDF NIFSKELSNE DINIVYEGQI
LRNVIKDYWG NPLKFDTEYY IINDNYIDRY IAPESNVLVL VQYPDRSKLY TGNPITIKSV
SDKNPYSRIL NGDNIILHML YNSRKYMIIR DTDTIYATQG GECSQNCVYA LKLQSNLGNY
GIGIFSIKNI VSKNKYCSQI FSSFRENTML LADIYKPWRF SFKNAYTPVA VTNYETKLLS
TSSFWKFISR DPGWVE


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640B Botulinum Neurotoxin Type F Light Chain, Recombinant1 100µg
LST620A Botulinum Neurotoxin Type B Light Chain, recombinant 10 ug.
610A Botulinum Neurotoxin Type A Light Chain, Recombinant1 10µg
LST630A Botulinum Neurotoxin Type D Light Chain, recombinant 10 ug.


 

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