DCOR_LEIDO
ID DCOR_LEIDO Reviewed; 707 AA.
AC P27116;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Ornithine decarboxylase;
DE Short=ODC;
DE EC=4.1.1.17;
OS Leishmania donovani.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5661;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1339439; DOI=10.1016/s0021-9258(18)45885-1;
RA Hanson S.S., Adelman J., Ullman B.;
RT "Amplification and molecular cloning of the ornithine decarboxylase gene of
RT Leishmania donovani.";
RL J. Biol. Chem. 267:2350-2359(1992).
RN [2]
RP ACTIVITY REGULATION.
RX PubMed=3098971; DOI=10.1111/j.1550-7408.1986.tb05654.x;
RA Kaur K., Emmett K., McCann P.P., Sjoerdsma A., Ullman B.;
RT "Effects of DL-alpha-difluoromethylornithine on Leishmania donovani
RT promastigotes.";
RL J. Protozool. 33:518-521(1986).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=7947774; DOI=10.1021/bi00250a016;
RA Osterman A., Grishin N.V., Kinch L.N., Phillips M.A.;
RT "Formation of functional cross-species heterodimers of ornithine
RT decarboxylase.";
RL Biochemistry 33:13662-13667(1994).
RN [4]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17407445; DOI=10.1042/bj20070188;
RA Dufe V.T., Ingner D., Heby O., Khomutov A.R., Persson L., Al-Karadaghi S.;
RT "A structural insight into the inhibition of human and Leishmania donovani
RT ornithine decarboxylases by 1-amino-oxy-3-aminopropane.";
RL Biochem. J. 405:261-268(2007).
CC -!- FUNCTION: Catalyzes the first and rate-limiting step of polyamine
CC biosynthesis that converts ornithine into putrescine, which is the
CC precursor for the polyamines, spermidine and spermine. Polyamines are
CC essential for cell proliferation and are implicated in cellular
CC processes, ranging from DNA replication to apoptosis.
CC {ECO:0000269|PubMed:17407445, ECO:0000269|PubMed:7947774}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-ornithine = CO2 + putrescine; Xref=Rhea:RHEA:22964,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:46911,
CC ChEBI:CHEBI:326268; EC=4.1.1.17;
CC Evidence={ECO:0000269|PubMed:7947774};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P11926};
CC -!- ACTIVITY REGULATION: Inhibited by antizyme (AZ) in response to
CC polyamine levels. AZ inhibits the assembly of the functional homodimer
CC by binding to ODC monomers and targeting them for ubiquitin-independent
CC proteolytic destruction by the 26S proteasome (By similarity).
CC Inhibited by 1-amino-oxy-3-aminopropane (APA, an isosteric analog of
CC putrescine) (PubMed:17407445). Irreversibly inhibited by alpha-
CC difluoromethylornithine (DFMO, a curative agent of West African
CC sleeping sickness) (PubMed:3098971, PubMed:17407445).
CC {ECO:0000250|UniProtKB:P11926, ECO:0000269|PubMed:17407445,
CC ECO:0000269|PubMed:3098971}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.39 mM for L-ornithine {ECO:0000269|PubMed:17407445};
CC Note=kcat is 8.1 sec(-1) with L-ornithine as substrate.
CC {ECO:0000269|PubMed:17407445};
CC -!- PATHWAY: Amine and polyamine biosynthesis; putrescine biosynthesis via
CC L-ornithine pathway; putrescine from L-ornithine: step 1/1.
CC -!- SUBUNIT: Homodimer. Only the dimer is catalytically active, as the
CC active sites are constructed of residues from both monomers.
CC {ECO:0000269|PubMed:7947774}.
CC -!- SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family.
CC {ECO:0000305}.
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DR EMBL; M81192; AAA29259.1; -; Genomic_DNA.
DR PIR; A42322; A42322.
DR AlphaFoldDB; P27116; -.
DR SMR; P27116; -.
DR ChEMBL; CHEMBL6192; -.
DR VEuPathDB; TriTrypDB:LdBPK_120105.1; -.
DR VEuPathDB; TriTrypDB:LdCL_120007900; -.
DR VEuPathDB; TriTrypDB:LDHU3_12.0390; -.
DR BRENDA; 4.1.1.17; 2947.
DR SABIO-RK; P27116; -.
DR UniPathway; UPA00535; UER00288.
DR GO; GO:0004586; F:ornithine decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0033387; P:putrescine biosynthetic process from ornithine; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR022643; De-COase2_C.
DR InterPro; IPR022657; De-COase2_CS.
DR InterPro; IPR022644; De-COase2_N.
DR InterPro; IPR022653; De-COase2_pyr-phos_BS.
DR InterPro; IPR000183; Orn/DAP/Arg_de-COase.
DR InterPro; IPR002433; Orn_de-COase.
DR InterPro; IPR029066; PLP-binding_barrel.
DR PANTHER; PTHR11482; PTHR11482; 1.
DR Pfam; PF02784; Orn_Arg_deC_N; 1.
DR Pfam; PF00278; Orn_DAP_Arg_deC; 1.
DR PRINTS; PR01179; ODADCRBXLASE.
DR PRINTS; PR01182; ORNDCRBXLASE.
DR SUPFAM; SSF50621; SSF50621; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
DR PROSITE; PS00878; ODR_DC_2_1; 1.
DR PROSITE; PS00879; ODR_DC_2_2; 1.
PE 1: Evidence at protein level;
KW Decarboxylase; Lyase; Polyamine biosynthesis; Pyridoxal phosphate.
FT CHAIN 1..707
FT /note="Ornithine decarboxylase"
FT /id="PRO_0000149901"
FT REGION 83..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 634
FT /note="Proton donor; shared with dimeric partner"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 421
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 458
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 498..501
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 561..562
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 635
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 663
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT SITE 418
FT /note="Stacks against the aromatic ring of pyridoxal
FT phosphate and stabilizes reaction intermediates"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT MOD_RES 288
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P11926"
SQ SEQUENCE 707 AA; 77397 MW; EBDF14F791EC572D CRC64;
MGDHDVALCH VSRYNHANYW AFVPLPTVSD DTGCDSLHHD SASERIRMAP PASASKAGAA
EERLHPYERR LLDQYQIHLQ PANRNPLSRA DSAAGREETA QTPAQVQMVP VVAVADSTSD
QHASVASSQD LVDLFFLEGS QAVDGLCFSP YPIYGWRTAE ERRAAVCEVF KTYNVVTRLP
ASPAALAAAQ RRYSRHRHSA IAPINKSAIE TREQYWRRLS NLYTQKGVKD AASAADAAAT
TATNGAVPAA PAYEPEDPFY IIDLGRVVEQ MARWRHELPM VRPYFAVKSN PQPAVLEVLS
ALGAGFDCAS KEEIHMVLGR QLVASPDDII FANPCKQLGD LREAQACGVT YVTVDNPLEM
EKISRLMPSA HAIIRIKTND SKAQCSFSTK FGAPLEDVEG LLEAARQFNV TVCGVSFHVG
SGNDDQSAYV SAVRDAYQVF QQAVQYGFKC TILDIGGGFP GTEVVEGSGN TSFEAIARTI
RPVLAELFGG GDVTIISEPG RYFTAASHAL LMNVFASRTL RLSDVEVSRQ AFQSVVSMDE
PEEYQYYVND GLYHSFNCIL FDHAHPTLLL LNDGDGADGV ESGTEAAAVC SEEEGETSLS
GPLANDPLFM SAWDRRRSFA RRPLRITTIF GPTCDSMDCI LKKQPFPEMK LGDWLLVPDM
GSYTTAAAGF FNGFATRRLE WVSSVDLCAR PRPVYTREGN TLRCVSE
