VM1LA_BOTLC
ID VM1LA_BOTLC Reviewed; 202 AA.
AC P84907;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Snake venom metalloproteinase leucurolysin-A;
DE Short=Leuc-A;
DE Short=SVMP;
DE EC=3.4.24.-;
OS Bothrops leucurus (Whitetail lancehead).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=157295;
RN [1]
RP PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, PYROGLUTAMATE
RP FORMATION AT GLN-1, AND CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=19652343; DOI=10.1107/s1744309109025767;
RA Ferreira R.N., Rates B., Richardson M., Guimaraes B.G., Sanchez E.O.,
RA Pimenta A.M., Nagem R.A.;
RT "Complete amino-acid sequence, crystallization and preliminary X-ray
RT diffraction studies of leucurolysin-a, a nonhaemorrhagic metalloproteinase
RT from Bothrops leucurus snake venom.";
RL Acta Crystallogr. F 65:798-801(2009).
RN [2]
RP PROTEIN SEQUENCE OF 4-202, FUNCTION, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=16139412; DOI=10.1016/j.biochi.2005.07.008;
RA Bello C.A., Hermogenes A.L.N., Magalhaes A., Veiga S.S., Gremski L.H.,
RA Richardson M., Sanchez E.F.;
RT "Isolation and biochemical characterization of a fibrinolytic proteinase
RT from Bothrops leucurus (white-tailed jararaca) snake venom.";
RL Biochimie 88:189-200(2006).
RN [3]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=17482228; DOI=10.1016/j.toxicon.2007.03.002;
RA Gremski L.H., Chaim O.M., Paludo K.S., Sade Y.B., Otuki M.F.,
RA Richardson M., Gremski W., Sanchez E.F., Veiga S.S.;
RT "Cytotoxic, thrombolytic and edematogenic activities of leucurolysin-a, a
RT metalloproteinase from Bothrops leucurus snake venom.";
RL Toxicon 50:120-134(2007).
CC -!- FUNCTION: Non-hemorrhagic metalloproteinase that hydrolyzes the alpha
CC chains of fibrinogen, as well as fibrin, fibronectin and casein. Beta
CC and gamma chains are also hydrolyzed, but more slowly. Thrombolytic
CC activity is also observed. Induces detachment of endothelial cells
CC followed by death, and inhibits endothelial cell adhesion to
CC fibronectin. Induces edema in mouse paw. Inhibits ADP-induced platelet
CC aggregation on human platelet-rich plasma with an IC(50) of 2.8 uM.
CC {ECO:0000269|PubMed:16139412, ECO:0000269|PubMed:17482228}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and 2-mercaptoethanol. Inhibited
CC by 1 mM zinc ion and to a lesser extent by 1 mM calcium ion.
CC {ECO:0000269|PubMed:16139412}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0 for dimethylcasein with a complete loss of activity
CC above pH 11.0. {ECO:0000269|PubMed:16139412};
CC Temperature dependence:
CC Optimum temperature is 30-40 degrees Celsius with a complete loss of
CC activity above 60 degrees Celsius. {ECO:0000269|PubMed:16139412};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16139412}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16139412}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16139412}.
CC -!- MISCELLANEOUS: Has no activity toward laminin (PubMed:16139412).
CC {ECO:0000305|PubMed:16139412}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-I
CC subfamily. {ECO:0000305}.
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DR PDB; 4Q1L; X-ray; 1.90 A; A=1-202.
DR PDBsum; 4Q1L; -.
DR AlphaFoldDB; P84907; -.
DR SMR; P84907; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0042730; P:fibrinolysis; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF01421; Reprolysin; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding; Metalloprotease;
KW Platelet aggregation inhibiting toxin; Protease;
KW Pyrrolidone carboxylic acid; Secreted; Toxin; Zinc.
FT CHAIN 1..202
FT /note="Snake venom metalloproteinase leucurolysin-A"
FT /id="PRO_0000249183"
FT DOMAIN 6..202
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 9
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 93
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:4Q1L"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:19652343"
FT DISULFID 117..197
FT /evidence="ECO:0007744|PDB:4Q1L"
FT DISULFID 157..181
FT /evidence="ECO:0007744|PDB:4Q1L"
FT DISULFID 159..164
FT /evidence="ECO:0007744|PDB:4Q1L"
FT CONFLICT 44
FT /note="F -> Y (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 122..135
FT /note="SVAVVMDHSKKNLR -> MVAWGQDY (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="T -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 6..14
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 16..21
FT /evidence="ECO:0007829|PDB:4Q1L"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 26..44
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:4Q1L"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 133..147
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:4Q1L"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 180..193
FT /evidence="ECO:0007829|PDB:4Q1L"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:4Q1L"
SQ SEQUENCE 202 AA; 23019 MW; B2C822D7F5835176 CRC64;
QQFSPRYIEL VVVADHGMFK KYNSNLNTIR KWVHEMLNTV NGFFRSMNVD ASLVNLEVWS
KKDLIKVEKD SSKTLTSFGE WRERDLLPRI SHDHAQLLTV IFLDEETIGI AYTAGMCDLS
QSVAVVMDHS KKNLRVAVTM AHELGHNLGM RHDGNQCHCN APSCIMADTL SKGLSFEFSD
CSQNQYQTYL TKHNPQCILN KP
