DCOR_TRYBB
ID DCOR_TRYBB Reviewed; 423 AA.
AC P07805;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Ornithine decarboxylase;
DE Short=ODC;
DE EC=4.1.1.17 {ECO:0000269|PubMed:10985770};
OS Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3036823; DOI=10.1016/s0021-9258(18)47475-3;
RA Phillips M.A., Coffino P., Wang C.C.;
RT "Cloning and sequencing of the ornithine decarboxylase gene from
RT Trypanosoma brucei. Implications for enzyme turnover and selective
RT difluoromethylornithine inhibition.";
RL J. Biol. Chem. 262:8721-8727(1987).
RN [2] {ECO:0007744|PDB:1QU4, ECO:0007744|PDB:2TOD}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP AND PYRIDOXALPHOSPHATE AT LYS-67.
RX PubMed=10563800; DOI=10.1021/bi9915115;
RA Grishin N.V., Osterman A.L., Brooks H.B., Phillips M.A., Goldsmith E.J.;
RT "X-ray structure of ornithine decarboxylase from Trypanosoma brucei: the
RT native structure and the structure in complex with alpha-
RT difluoromethylornithine.";
RL Biochemistry 38:15174-15184(1999).
RN [3] {ECO:0007744|PDB:1F3T}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH COFACTOR AND
RP PUTRESCINE, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP CYS-358.
RX PubMed=10985770; DOI=10.1021/bi001209s;
RA Jackson L.K., Brooks H.B., Osterman A.L., Goldsmith E.J., Phillips M.A.;
RT "Altering the reaction specificity of eukaryotic ornithine decarboxylase.";
RL Biochemistry 39:11247-11257(2000).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH COFACTOR AND
RP SUBSTRATE ANALOG.
RX PubMed=15476392; DOI=10.1021/bi048933l;
RA Jackson L.K., Baldwin J., Akella R., Goldsmith E.J., Phillips M.A.;
RT "Multiple active site conformations revealed by distant site mutation in
RT ornithine decarboxylase.";
RL Biochemistry 43:12990-12999(2004).
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:0000250|UniProtKB:P11926}.
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:10985770};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:10563800, ECO:0000269|PubMed:10985770,
CC ECO:0000269|PubMed:15476392};
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.
CC {ECO:0000250|UniProtKB:P11926}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=400 uM for L-ornithine {ECO:0000269|PubMed:10985770};
CC Note=kcat is 15 sec(-1) with L-ornithine as substrate.
CC {ECO:0000269|PubMed:10985770};
CC -!- PATHWAY: Amine and polyamine biosynthesis; putrescine biosynthesis via
CC L-ornithine pathway; putrescine from L-ornithine: step 1/1.
CC {ECO:0000305|PubMed:3036823}.
CC -!- SUBUNIT: Homodimer. Only the dimer is catalytically active, as the
CC active sites are constructed of residues from both monomers.
CC {ECO:0000250|UniProtKB:P11926}.
CC -!- SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA30218.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; J02771; AAA30218.1; ALT_INIT; Genomic_DNA.
DR EMBL; J02771; AAA30219.1; -; Genomic_DNA.
DR PDB; 1F3T; X-ray; 2.00 A; A/B/C/D=1-423.
DR PDB; 1QU4; X-ray; 2.90 A; A/B/C/D=1-423.
DR PDB; 1SZR; X-ray; 2.15 A; A/B/C/D=1-423.
DR PDB; 2TOD; X-ray; 2.00 A; A/B/C/D=1-423.
DR PDBsum; 1F3T; -.
DR PDBsum; 1QU4; -.
DR PDBsum; 1SZR; -.
DR PDBsum; 2TOD; -.
DR AlphaFoldDB; P07805; -.
DR SMR; P07805; -.
DR BRENDA; 4.1.1.17; 6519.
DR SABIO-RK; P07805; -.
DR UniPathway; UPA00535; UER00288.
DR EvolutionaryTrace; P07805; -.
DR GO; GO:0004586; F:ornithine decarboxylase activity; IDA:GeneDB.
DR GO; GO:0006596; P:polyamine biosynthetic process; TAS:GeneDB.
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; 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 3D-structure; Decarboxylase; Lyase; Polyamine biosynthesis;
KW Pyridoxal phosphate.
FT CHAIN 1..423
FT /note="Ornithine decarboxylase"
FT /id="PRO_0000149903"
FT ACT_SITE 358
FT /note="Proton donor; shared with dimeric partner"
FT /evidence="ECO:0000269|PubMed:10985770,
FT ECO:0000269|PubMed:15476392"
FT BINDING 198
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770, ECO:0000269|PubMed:15476392"
FT BINDING 235
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770, ECO:0000269|PubMed:15476392"
FT BINDING 272..275
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770, ECO:0000269|PubMed:15476392"
FT BINDING 329..330
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770"
FT BINDING 359
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770"
FT BINDING 387
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:10985770, ECO:0000269|PubMed:15476392"
FT SITE 195
FT /note="Stacks against the aromatic ring of pyridoxal
FT phosphate and stabilizes reaction intermediates"
FT /evidence="ECO:0000305|PubMed:10563800"
FT MOD_RES 67
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:10563800,
FT ECO:0000269|PubMed:15476392, ECO:0007744|PDB:1QU4"
FT MUTAGEN 358
FT /note="C->S,A: Converts the enzyme into a decarboxylation-
FT dependent transaminase, producing gamma-aminobutyaldehyde
FT (gamma-ABA) and pyridoxamine 5-phosphate (PMP) instead of
FT putrescine."
FT /evidence="ECO:0000269|PubMed:10985770"
FT HELIX 19..26
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 43..56
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 72..80
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 90..98
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 115..123
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2TOD"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 204..222
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:1SZR"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 246..260
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 282..293
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:1F3T"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:2TOD"
FT STRAND 348..354
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 363..371
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:1F3T"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:1F3T"
FT HELIX 414..418
FT /evidence="ECO:0007829|PDB:1F3T"
SQ SEQUENCE 423 AA; 46881 MW; 924A5AA6C4CD2C36 CRC64;
MDIVVNDDLS CRFLEGFNTR DALCKKISMN TCDEGDPFFV ADLGDIVRKH ETWKKCLPRV
TPFYAVKCND DWRVLGTLAA LGTGFDCASN TEIQRVRGIG VPPEKIIYAN PCKQISHIRY
ARDSGVDVMT FDCVDELEKV AKTHPKAKMV LRISTDDSLA RCRLSVKFGA KVEDCRFILE
QAKKLNIDVT GVSFHVGSGS TDASTFAQAI SDSRFVFDMG TELGFNMHIL DIGGGFPGTR
DAPLKFEEIA GVINNALEKH FPPDLKLTIV AEPGRYYVAS AFTLAVNVIA KKVTPGVQTD
VGAHAESNAQ SFMYYVNDGV YGSFNCILYD HAVVRPLPQR EPIPNEKLYP SSVWGPTCDG
LDQIVERYYL PEMQVGEWLL FEDMGAYTVV GTSSFNGFQS PTIYYVVSGL PDHVVRELKS
QKS
