DCAMC_TRYBB
ID DCAMC_TRYBB Reviewed; 370 AA.
AC P50244; A5HNV7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2017, sequence version 2.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=S-adenosylmethionine decarboxylase proenzyme;
DE Short=AdoMetDC;
DE Short=SAMDC;
DE EC=4.1.1.50 {ECO:0000269|PubMed:17485680, ECO:0000269|PubMed:18949025};
DE Contains:
DE RecName: Full=S-adenosylmethionine decarboxylase alpha chain;
DE Contains:
DE RecName: Full=S-adenosylmethionine decarboxylase beta chain;
DE Flags: Precursor;
OS Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, INTERACTION WITH
RP ADOMETDC PROZYME, PROTEOLYTIC CLEAVAGE, AND DEVELOPMENTAL STAGE.
RC STRAIN=427;
RX PubMed=17485680; DOI=10.1073/pnas.0701111104;
RA Willert E.K., Fitzpatrick R., Phillips M.A.;
RT "Allosteric regulation of an essential trypanosome polyamine biosynthetic
RT enzyme by a catalytically dead homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8275-8280(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=EATRO 164;
RA Scott J.R., Ullman B.;
RT "Molecular cloning and functional expression of the S-adenosylmethionine
RT decarboxylase gene of Leishmania donovani and Trypanosoma brucei.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=18949025; DOI=10.1371/journal.ppat.1000183;
RA Willert E.K., Phillips M.A.;
RT "Regulated expression of an essential allosteric activator of polyamine
RT biosynthesis in African trypanosomes.";
RL PLoS Pathog. 4:E1000183-E1000183(2008).
CC -!- FUNCTION: In association with the catalytically inactive AdoMetDC
CC prozyme, catalyzes the decarboxylation of S-adenosyl-L-methionine which
CC is essential for the biosynthesis of the polyamine spermidine. Required
CC for growth and survival during the bloodstream life cycle stage
CC (PubMed:18949025). {ECO:0000269|PubMed:17485680,
CC ECO:0000269|PubMed:18949025}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + S-adenosyl-L-methionine = CO2 + S-adenosyl 3-
CC (methylsulfanyl)propylamine; Xref=Rhea:RHEA:15981, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57443, ChEBI:CHEBI:59789; EC=4.1.1.50;
CC Evidence={ECO:0000269|PubMed:17485680, ECO:0000269|PubMed:18949025};
CC -!- COFACTOR:
CC Name=pyruvate; Xref=ChEBI:CHEBI:15361;
CC Note=Binds 1 pyruvoyl group covalently per subunit.;
CC -!- ACTIVITY REGULATION: Allosterically activated by AdoMetDC prozyme.
CC Activated by putrescine and to a lesser extent by spermidine,
CC norspermidine and spermine. Inhibited by 5'-([(Z)-4-amino-2-
CC butenyl]methylamino)-5'-deoxyadenosine (MDL 73811).
CC {ECO:0000269|PubMed:17485680}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.38 mM for S-adenosyl-L-methionine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:17485680};
CC KM=0.24 mM for S-adenosyl-L-methionine (in presence of putrescine and
CC at 37 degrees Celsius) {ECO:0000269|PubMed:17485680};
CC KM=0.11 mM for S-adenosyl-L-methionine (in presence of AdoMetDC
CC prozyme and at 37 degrees Celsius) {ECO:0000269|PubMed:17485680};
CC KM=0.17 mM for S-adenosyl-L-methionine (in presence of AdoMetDC
CC prozyme and putrescine and at 37 degrees Celsius)
CC {ECO:0000269|PubMed:17485680};
CC -!- PATHWAY: Amine and polyamine biosynthesis; S-adenosylmethioninamine
CC biosynthesis; S-adenosylmethioninamine from S-adenosyl-L-methionine:
CC step 1/1. {ECO:0000269|PubMed:17485680, ECO:0000269|PubMed:18949025}.
CC -!- SUBUNIT: Forms a heterodimer with catalytically inactive AdoMetDC
CC prozyme; heterodimerization is required to activate AdoMetDC.
CC {ECO:0000269|PubMed:17485680}.
CC -!- DEVELOPMENTAL STAGE: Expressed during both bloodstream (BF) and
CC procyclic insect (PF) life cycle stages. {ECO:0000269|PubMed:17485680}.
CC -!- PTM: Is synthesized initially as an inactive proenzyme
CC (PubMed:17485680). Formation of the active enzyme involves a self-
CC maturation process in which the active site pyruvoyl group is generated
CC from an internal serine residue via an autocatalytic post-translational
CC modification (By similarity). Two non-identical subunits are generated
CC from the proenzyme in this reaction, and the pyruvate is formed at the
CC N-terminus of the alpha chain, which is derived from the carboxyl end
CC of the proenzyme (By similarity). The post-translation cleavage follows
CC an unusual pathway, termed non-hydrolytic serinolysis, in which the
CC side chain hydroxyl group of the serine supplies its oxygen atom to
CC form the C-terminus of the beta chain, while the remainder of the
CC serine residue undergoes an oxidative deamination to produce ammonia
CC and the pyruvoyl group blocking the N-terminus of the alpha chain (By
CC similarity). {ECO:0000250|UniProtKB:P17707,
CC ECO:0000269|PubMed:17485680}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes cell growth arrest
CC followed by death. Putrescine levels are increased and the production
CC of spermidine, glutathionyl-spermidine and trypanothione is severely
CC reduced. In addition, expression levels of AdoMetDC prozyme and
CC ornithine carboxylase (ODC) are increased.
CC {ECO:0000269|PubMed:18949025}.
CC -!- SIMILARITY: Belongs to the eukaryotic AdoMetDC family. {ECO:0000305}.
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DR EMBL; EF545595; ABQ23690.1; -; mRNA.
DR EMBL; U20092; AAA61969.1; -; Genomic_DNA.
DR AlphaFoldDB; P50244; -.
DR SMR; P50244; -.
DR ChEMBL; CHEMBL4105987; -.
DR EnsemblProtists; AAZ11999; AAZ11999; Tb927.6.4410.
DR EnsemblProtists; AAZ12004; AAZ12004; Tb927.6.4460.
DR OMA; LEIWFEE; -.
DR BRENDA; 4.1.1.50; 6519.
DR SABIO-RK; P50244; -.
DR UniPathway; UPA00331; UER00451.
DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB.
DR GO; GO:0004014; F:adenosylmethionine decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:1901307; P:positive regulation of spermidine biosynthetic process; IMP:UniProtKB.
DR GO; GO:1905724; P:positive regulation of trypanothione biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006557; P:S-adenosylmethioninamine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046499; P:S-adenosylmethioninamine metabolic process; IMP:UniProtKB.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; IDA:UniProtKB.
DR GO; GO:0008295; P:spermidine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006597; P:spermine biosynthetic process; IEA:InterPro.
DR InterPro; IPR001985; S-AdoMet_decarboxylase.
DR InterPro; IPR016067; S-AdoMet_deCO2ase_core.
DR InterPro; IPR018166; S-AdoMet_deCO2ase_CS.
DR PANTHER; PTHR11570; PTHR11570; 1.
DR Pfam; PF01536; SAM_decarbox; 1.
DR PIRSF; PIRSF001355; S-AdenosylMet_decarboxylase; 1.
DR SUPFAM; SSF56276; SSF56276; 1.
DR PROSITE; PS01336; ADOMETDC; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Decarboxylase; Lyase; Polyamine biosynthesis;
KW Pyruvate; S-adenosyl-L-methionine; Schiff base; Spermidine biosynthesis;
KW Zymogen.
FT CHAIN 1..85
FT /note="S-adenosylmethionine decarboxylase beta chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000029983"
FT CHAIN 86..370
FT /note="S-adenosylmethionine decarboxylase alpha chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000029984"
FT ACT_SITE 29
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT ACT_SITE 32
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT ACT_SITE 86
FT /note="Schiff-base intermediate with substrate; via pyruvic
FT acid"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT ACT_SITE 100
FT /note="Proton donor; for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT ACT_SITE 249
FT /note="Proton acceptor; for processing activity"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT ACT_SITE 262
FT /note="Proton acceptor; for processing activity"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT BINDING 28
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT BINDING 85
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT BINDING 266
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT SITE 85..86
FT /note="Cleavage (non-hydrolytic); by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT MOD_RES 86
FT /note="Pyruvic acid (Ser); by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P17707"
FT CONFLICT 177..178
FT /note="FH -> LD (in Ref. 1; ABQ23690)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 370 AA; 41748 MW; 6633B7DE983E41A9 CRC64;
MSSCKDSLSL MAMWGSIARF DPKHERSFEG PEKRLEVIMR VVDGTHVSGL LAHDDDVWQK
VIDAICAHIV SREFNEYIRS YVLSESSLFV MKDRVILITC GTITLLNCVP LICEAVSTVC
GEVEWVSFMH KNYSFPWEQK GPHLSMAEEF KTLRSHFPSG QPFIFGPIDS DHYFLYFHSD
VVQPSCSDDA QLSMTMYGLD RNQTKHWYSD KMLPTGPETA VIREATGLSE VVDDSWILHD
LQYEPCGYSI NAIRGSEYQT IHITPEEHCS FASYETNTCA LNYSKCICGV LRVFDPERFS
VIVFIDPDSA VGKSYHSGGT IGVEPEYYPN YEAHHRTVNE YTPGHWVLKV NYVKRAVGTV
GTSAASGAKE
