DCDB_MYCTU
ID DCDB_MYCTU Reviewed; 190 AA.
AC P9WP17; L0T3B0; O07247;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=dCTP deaminase, dUMP-forming {ECO:0000255|HAMAP-Rule:MF_00146, ECO:0000305};
DE EC=3.5.4.30 {ECO:0000255|HAMAP-Rule:MF_00146, ECO:0000269|PubMed:18164314};
DE AltName: Full=Bifunctional dCTP deaminase:dUTPase {ECO:0000255|HAMAP-Rule:MF_00146, ECO:0000303|PubMed:18164314};
DE AltName: Full=DCD-DUT {ECO:0000255|HAMAP-Rule:MF_00146};
GN Name=dcd {ECO:0000255|HAMAP-Rule:MF_00146}; OrderedLocusNames=Rv0321;
GN ORFNames=MTCY63.26;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3] {ECO:0007744|PDB:2QLP, ECO:0007744|PDB:2QXX}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP DTTP, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=18164314; DOI=10.1016/j.jmb.2007.11.099;
RA Helt S.S., Thymark M., Harris P., Aagaard C., Dietrich J., Larsen S.,
RA Willemoes M.;
RT "Mechanism of dTTP inhibition of the bifunctional dCTP deaminase:dUTPase
RT encoded by Mycobacterium tuberculosis.";
RL J. Mol. Biol. 376:554-569(2008).
RN [4] {ECO:0007744|PDB:4A6A}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF MUTANT VAL-115 IN COMPLEX WITH
RP DTTP.
RA Lovgreen M.N., Harris P., Ucar E., Willemoes M.;
RT "Dttp inhibition of the bifunctional Dctp deaminase- dutpase from
RT Mycobacterium tuberculosis is pH dependent: kinetic analyses and crystal
RT structure of A115V Variant.";
RL Submitted (NOV-2011) to the PDB data bank.
CC -!- FUNCTION: Bifunctional enzyme that catalyzes both the deamination of
CC dCTP to dUTP and the hydrolysis of dUTP to dUMP without releasing the
CC toxic dUTP intermediate. It also acts as a dUTP diphosphatase. Affinity
CC for dCTP and dUTP are very similar. {ECO:0000269|PubMed:18164314}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dCTP + 2 H2O = diphosphate + dUMP + NH4(+);
CC Xref=Rhea:RHEA:19205, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61481, ChEBI:CHEBI:246422;
CC EC=3.5.4.30; Evidence={ECO:0000255|HAMAP-Rule:MF_00146,
CC ECO:0000269|PubMed:18164314};
CC -!- ACTIVITY REGULATION: dTTP inhibits both the combined reaction and the
CC dUTPase reaction. {ECO:0000269|PubMed:18164314}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 0.18 sec(-1) with dCTP as substrate. kcat is 0.33 sec(-
CC 1) with dUTP as substrate. {ECO:0000269|PubMed:18164314};
CC -!- PATHWAY: Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP: step
CC 1/1. {ECO:0000255|HAMAP-Rule:MF_00146, ECO:0000305}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000255|HAMAP-Rule:MF_00146,
CC ECO:0000269|PubMed:18164314}.
CC -!- SIMILARITY: Belongs to the dCTP deaminase family. {ECO:0000255|HAMAP-
CC Rule:MF_00146}.
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DR EMBL; AL123456; CCP43051.1; -; Genomic_DNA.
DR PIR; B70526; B70526.
DR RefSeq; NP_214835.1; NC_000962.3.
DR RefSeq; WP_003898399.1; NZ_NVQJ01000026.1.
DR PDB; 2QLP; X-ray; 2.47 A; A/B/C/D/E/F=1-161.
DR PDB; 2QXX; X-ray; 2.00 A; A/B=1-190.
DR PDB; 4A6A; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=1-190.
DR PDBsum; 2QLP; -.
DR PDBsum; 2QXX; -.
DR PDBsum; 4A6A; -.
DR AlphaFoldDB; P9WP17; -.
DR SMR; P9WP17; -.
DR IntAct; P9WP17; 5.
DR MINT; P9WP17; -.
DR STRING; 83332.Rv0321; -.
DR PaxDb; P9WP17; -.
DR DNASU; 886552; -.
DR GeneID; 45424289; -.
DR GeneID; 886552; -.
DR KEGG; mtu:Rv0321; -.
DR TubercuList; Rv0321; -.
DR eggNOG; COG0717; Bacteria.
DR OMA; FENHRYP; -.
DR PhylomeDB; P9WP17; -.
DR BRENDA; 3.5.4.13; 3445.
DR UniPathway; UPA00610; UER00667.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0033973; F:dCTP deaminase (dUMP-forming) activity; IDA:MTBBASE.
DR GO; GO:0008829; F:dCTP deaminase activity; IBA:GO_Central.
DR GO; GO:0004170; F:dUTP diphosphatase activity; IDA:MTBBASE.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0006226; P:dUMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006229; P:dUTP biosynthetic process; IEA:InterPro.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; IBA:GO_Central.
DR CDD; cd07557; trimeric_dUTPase; 1.
DR Gene3D; 2.70.40.10; -; 1.
DR HAMAP; MF_00146; dCTP_deaminase; 1.
DR InterPro; IPR011962; dCTP_deaminase.
DR InterPro; IPR029054; dUTPase-like.
DR InterPro; IPR036157; dUTPase-like_sf.
DR InterPro; IPR033704; dUTPase_trimeric.
DR Pfam; PF00692; dUTPase; 1.
DR SUPFAM; SSF51283; SSF51283; 1.
DR TIGRFAMs; TIGR02274; dCTP_deam; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Nucleotide metabolism; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..190
FT /note="dCTP deaminase, dUMP-forming"
FT /id="PRO_0000155997"
FT REGION 160..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 129
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28248, ECO:0000255|HAMAP-
FT Rule:MF_00146"
FT BINDING 101..106
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|Ref.4"
FT BINDING 119
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314, ECO:0000305|Ref.4"
FT BINDING 127..129
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314, ECO:0000305|Ref.4"
FT BINDING 148
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|Ref.4"
FT BINDING 162
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314, ECO:0000305|Ref.4"
FT BINDING 170
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314, ECO:0000305|Ref.4"
FT BINDING 174
FT /ligand="dCTP"
FT /ligand_id="ChEBI:CHEBI:61481"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314, ECO:0000305|Ref.4"
FT SITE 116..117
FT /note="Important for bifunctional activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00146,
FT ECO:0000305|PubMed:18164314"
FT HELIX 5..13
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:2QXX"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4A6A"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 79..89
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:2QXX"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:2QXX"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2QXX"
FT STRAND 144..153
FT /evidence="ECO:0007829|PDB:2QXX"
FT TURN 165..168
FT /evidence="ECO:0007829|PDB:2QXX"
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:2QXX"
SQ SEQUENCE 190 AA; 20870 MW; F409329810B64781 CRC64;
MLLSDRDLRA EISSGRLGID PFDDTLVQPS SIDVRLDCLF RVFNNTRYTH IDPAKQQDEL
TSLVQPVDGE PFVLHPGEFV LGSTLELFTL PDNLAGRLEG KSSLGRLGLL THSTAGFIDP
GFSGHITLEL SNVANLPITL WPGMKIGQLC MLRLTSPSEH PYGSSRAGSK YQGQRGPTPS
RSYQNFIRST
