ID   PDE_CRODO               Reviewed;         829 AA.
AC   P0DQQ4;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   02-JUN-2021, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Venom phosphodiesterase CdcPDE {ECO:0000303|PubMed:33636276};
DE            Short=PDE;
DE            EC=3.6.1.- {ECO:0000250|UniProtKB:W8E7D1};
OS   Crotalus durissus collilineatus (Brazilian rattlesnake).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX   NCBI_TaxID=221569;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL
RP   PROPERTIES, 3D-STRUCTURE MODELING, SUBUNIT, MASS SPECTROMETRY, AND
RP   GLYCOSYLATION AT ASN-194 AND ASN-237.
RC   TISSUE=Venom;
RX   PubMed=33636276; DOI=10.1016/j.ijbiomac.2021.02.120;
RA   Oliveira I.S., Pucca M.B., Wiezel G.A., Cardoso I.A., Bordon K.C.F.,
RA   Sartim M.A., Kalogeropoulos K., Ahmadi S., Baiwir D., Nonato M.C.,
RA   Sampaio S.V., Laustsen A.H., Auf dem Keller U., Quinton L., Arantes E.C.;
RT   "Unraveling the structure and function of CdcPDE: A novel phosphodiesterase
RT   from Crotalus durissus collilineatus snake venom.";
RL   Int. J. Biol. Macromol. 178:180-192(2021).
CC   -!- FUNCTION: Hydrolyzes ADP with high activity. Shows weak or no activity
CC       on 5'-AMP, 5'-GMP, 3'-AMP, ATP, cAMP, and cGMP (By similarity). Is
CC       devoid of monophosphatase and proteinase activities (By similarity).
CC       Inhibits ADP-induced platelet aggregation and is cytotoxic to human
CC       keratinocytes (PubMed:33636276). Kinetic parameters indicated a higher
CC       affinity for the substrate bis(p-nitrophenyl) phosphate compared to
CC       others snake venom PDEs (PubMed:33636276). Is recognized by the
CC       crotalid antivenom produced by the Instituto Butantan
CC       (PubMed:33636276). {ECO:0000250|UniProtKB:W8E7D1,
CC       ECO:0000269|PubMed:33636276}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ADP + H2O = AMP + H(+) + phosphate; Xref=Rhea:RHEA:61436,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000250|UniProtKB:W8E7D1};
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000250|UniProtKB:W8E7D1};
CC       Note=Binds 2 divalent metal cations per subunit.
CC       {ECO:0000250|UniProtKB:W8E7D1};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.38 mM for bis(p-nitrophenyl) phosphate
CC         {ECO:0000269|PubMed:33636276};
CC       pH dependence:
CC         Optimum pH is 8.0-8.5. {ECO:0000269|PubMed:33636276};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.
CC         {ECO:0000269|PubMed:33636276};
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:33636276}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33636276}.
CC   -!- TISSUE SPECIFICITY: Expressed by venom gland.
CC       {ECO:0000305|PubMed:33636276}.
CC   -!- PTM: N-glycosylated. Glycosylation counts for an increased mass of ~9%.
CC       {ECO:0000269|PubMed:33636276}.
CC   -!- PTM: Contains 16 disulfide bonds. {ECO:0000305|PubMed:33636276}.
CC   -!- MASS SPECTROMETRY: Mass=100330; Method=MALDI; Note=Isoform/Glycoform-
CC       1.; Evidence={ECO:0000269|PubMed:33636276};
CC   -!- MASS SPECTROMETRY: Mass=105598; Method=MALDI; Note=Isoform/Glycoform-
CC       2.; Evidence={ECO:0000269|PubMed:33636276};
CC   -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC       family. {ECO:0000305}.
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DR   AlphaFoldDB; P0DQQ4; -.
DR   SMR; P0DQQ4; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.570.10; -; 1.
DR   Gene3D; 3.40.720.10; -; 1.
DR   InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR   InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR   InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR   InterPro; IPR020821; Extracellular_endonuc_su_A.
DR   InterPro; IPR044925; His-Me_finger_sf.
DR   InterPro; IPR002591; Phosphodiest/P_Trfase.
DR   InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR   InterPro; IPR001212; Somatomedin_B_dom.
DR   Pfam; PF01223; Endonuclease_NS; 1.
DR   Pfam; PF01663; Phosphodiest; 1.
DR   Pfam; PF01033; Somatomedin_B; 2.
DR   SMART; SM00892; Endonuclease_NS; 1.
DR   SMART; SM00477; NUC; 1.
DR   SMART; SM00201; SO; 2.
DR   SUPFAM; SSF53649; SSF53649; 1.
DR   SUPFAM; SSF54060; SSF54060; 1.
DR   SUPFAM; SSF90188; SSF90188; 2.
DR   PROSITE; PS00524; SMB_1; 2.
DR   PROSITE; PS50958; SMB_2; 2.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW   Platelet aggregation inhibiting toxin; Repeat; Secreted; Toxin.
FT   CHAIN           1..829
FT                   /note="Venom phosphodiesterase CdcPDE"
FT                   /evidence="ECO:0000269|PubMed:33636276"
FT                   /id="PRO_0000453027"
FT   DOMAIN          8..51
FT                   /note="SMB 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DOMAIN          52..96
FT                   /note="SMB 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   MOTIF           36..38
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        163
FT                   /note="AMP-threonine intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         125
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         163
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         249
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   BINDING         283
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         287
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         287
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   BINDING         330
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   BINDING         331
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   BINDING         440
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04,
FT                   ECO:0000305|PubMed:33636276"
FT   CARBOHYD        17
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:33636276"
FT   CARBOHYD        237
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:33636276"
FT   CARBOHYD        383
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        572
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        652
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   DISULFID        12..29
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        12..16
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        16..47
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        27..40
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        27..29
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        33..39
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        40..47
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        56..73
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        56..61
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        61..91
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        71..84
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        71..73
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        77..83
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        84..91
FT                   /note="Alternate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT   DISULFID        102..148
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        110..322
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        338..435
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        386..771
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        519..577
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        532..632
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        534..617
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT   DISULFID        740..750
FT                   /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
SQ   SEQUENCE   829 AA;  94154 MW;  83444D25725BB5A8 CRC64;
     GLKEPVQPQV SCRYRCNETF SRMASGCSCD DKCTERQACC SDYEDTCVLP TQSWSCSKLR
     CGEKRIANVL CSCSEDCLEK KDCCTDYKTI CKGETSWLKD KCASSGATQC PAGFEQSPLI
     LFSMDGFRAG YLENWDSLMP NINKLKTCGT HAKYMRAVYP TKTFVNHYTI ATGLYPESHG
     IIDNNIYDVN LNLNFSLSSS TARNPAWWGG QPIWHTATYQ GLKAATYFWP GSEVKINGSY
     PTIFKNYDKS IPFEARVTEV LKWLDLPKAK RPDFFTLYIE EPDTTGHKYG PVSGEIIKAL
     QMADRTLGML MEGLKQRNLH NCVNLILLAD HGMEEISCDR LEYMANYFDN VDFFMYEGPA
     PRIRSKNVPK DFYTFDSEGI VKNLTCRKPK QYFKAYLSKD LPKRLHYANN IRIDKVNLMV
     DQQWMAVRDK KFTRCKGGTH GYDNEFKSMQ AIFLAHGPGF NEKNEVTSFE NIEVYNLMCD
     LLKLKPAPND GTHGSLNHLL KNPFYTPSPA KEQSSPLSCP FGPVPSPDVS GCKCSSITEL
     EKVNQRLNLN NQAKTESEAH NLPYGRPQVL QNHSKYCLLH QAKYISAYSQ DILMPLWSSY
     TIYRSTSTSV PPSASDCLRL DVRIPAAQSQ TCSNYQPDLT ITPGFLYPPN FNSSNFEQYD
     ALITSNIVPM FKGFTRLWNY FHTTLIPKYA RERDGLNVIS GPIFDYNYDG HFDSYDTIKQ
     HVSNTKIPIP THYFVVLTSC ENQINTPLNC LGPLKVLSFI LPHRPDNSES CADTSPENLW
     VEERIQIHTA RVRDVELLTG LNFYSGLKQP LPETLQLKTF LPIFVNPVN