DPYS_LACK1
ID DPYS_LACK1 Reviewed; 542 AA.
AC Q9P903;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Dihydropyrimidinase;
DE Short=DHP;
DE Short=DHPase;
DE EC=3.5.2.2 {ECO:0000269|PubMed:10656811};
DE AltName: Full=5,6-dihydropyrimidine amidohydrolase;
DE AltName: Full=Hydantoinase;
GN Name=PYD2;
OS Lachancea kluyveri (strain ATCC 58438 / CBS 3082 / BCRC 21498 / NBRC 1685 /
OS JCM 7257 / NCYC 543 / NRRL Y-12651) (Yeast) (Saccharomyces kluyveri).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Lachancea.
OX NCBI_TaxID=226302;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-11, FUNCTION,
RP SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND INDUCTION.
RC STRAIN=ATCC 58438 / CBS 3082 / BCRC 21498 / NBRC 1685 / JCM 7257 / NCYC 543
RC / NRRL Y-12651;
RX PubMed=10656811; DOI=10.1006/jmbi.1999.3393;
RA Gojkovic Z., Jahnke K., Schnackerz K.D., Piskur J.;
RT "PYD2 encodes 5,6-dihydropyrimidine amidohydrolase, which participates in a
RT novel fungal catabolic pathway.";
RL J. Mol. Biol. 295:1073-1087(2000).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 2-542 IN COMPLEXES WITH ZINC
RP IONS; SUBSTRATE AND PRODUCT, CARBOXYLATION AT LYS-167, AND SUBUNIT.
RX PubMed=16517602; DOI=10.1074/jbc.m513266200;
RA Lohkamp B., Andersen B., Piskur J., Dobritzsch D.;
RT "The crystal structures of dihydropyrimidinases reaffirm the close
RT relationship between cyclic amidohydrolases and explain their substrate
RT specificity.";
RL J. Biol. Chem. 281:13762-13776(2006).
CC -!- FUNCTION: Catalyzes the second step of the reductive pyrimidine
CC degradation, the reversible hydrolytic ring opening of
CC dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil
CC to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino
CC isobutyrate. {ECO:0000269|PubMed:10656811}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,6-dihydrouracil + H2O = 3-(carbamoylamino)propanoate + H(+);
CC Xref=Rhea:RHEA:16121, ChEBI:CHEBI:11892, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15901; EC=3.5.2.2;
CC Evidence={ECO:0000269|PubMed:10656811};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:16517602};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:16517602};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.6 mM for dihydrouracil {ECO:0000269|PubMed:10656811};
CC KM=0.235 mM for dihydrothymine {ECO:0000269|PubMed:10656811};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10656811,
CC ECO:0000269|PubMed:16517602}.
CC -!- INDUCTION: Up-regulated by dihydrouracil and N-carbamyl-beta-alanine.
CC Detectable only in cells grown on dihydrouracil and N-carbamyl-beta-
CC alanine as sole nitrogen source. {ECO:0000269|PubMed:10656811}.
CC -!- PTM: Carboxylation allows a single lysine to coordinate two zinc ions.
CC {ECO:0000269|PubMed:16517602}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Hydantoinase/dihydropyrimidinase family. {ECO:0000305}.
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DR EMBL; AF156967; AAF69237.1; -; Genomic_DNA.
DR PDB; 2FTY; X-ray; 2.40 A; A/B/C/D=2-542.
DR PDB; 2FVK; X-ray; 2.40 A; A/B/C/D=2-542.
DR PDB; 2FVM; X-ray; 2.45 A; A/B/C/D=2-542.
DR PDBsum; 2FTY; -.
DR PDBsum; 2FVK; -.
DR PDBsum; 2FVM; -.
DR AlphaFoldDB; Q9P903; -.
DR SMR; Q9P903; -.
DR BRENDA; 3.5.2.2; 6897.
DR SABIO-RK; Q9P903; -.
DR EvolutionaryTrace; Q9P903; -.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0004157; F:dihydropyrimidinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046483; P:heterocycle metabolic process; IEA:UniProt.
DR GO; GO:1901360; P:organic cyclic compound metabolic process; IEA:UniProt.
DR CDD; cd01314; D-HYD; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR011778; Hydantoinase/dihydroPyrase.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hydrolase; Metal-binding; Zinc.
FT CHAIN 1..542
FT /note="Dihydropyrimidinase"
FT /id="PRO_0000313804"
FT BINDING 62
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /note="via carbamate group"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /note="via carbamate group"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FVK"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 255
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 331
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FVK"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT BINDING 392
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FVK"
FT MOD_RES 167
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000269|PubMed:16517602,
FT ECO:0007744|PDB:2FTY, ECO:0007744|PDB:2FVK,
FT ECO:0007744|PDB:2FVM"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 30..36
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 109..121
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 127..135
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 143..161
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 165..172
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 203..215
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 223..226
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 230..246
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 259..270
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 324..328
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 340..348
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 373..376
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 400..407
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 408..412
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 417..424
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 426..431
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:2FTY"
FT TURN 443..445
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 450..453
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 472..474
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:2FVK"
FT TURN 482..485
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 492..497
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 500..504
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:2FTY"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:2FTY"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:2FTY"
SQ SEQUENCE 542 AA; 60240 MW; E8758452CBE86E98 CRC64;
MPIYDLIIKN GIICTASDIY AAEIAVNNGK VQLIAASIDP SLGSEVIDAE GAFITPGGID
AHVHVDEPLK LLGDVVDTME HATRSAVAGG TTTVVAFSTQ DVSKKGPSAL AESVKLDVDE
YSEQTLYCDY GLHLILFQIE KPSVEARELL DVQLQAAYND YGVSSVKMFM TYPGLQISDY
DIMSAMYATR KNGFTTMLHA ENGDMVKWMI EALEEQGLTD AYYHGVSRPS IVEGEATNRA
ITLATTMDTP ILFVHVSSPQ AAEVIKQAQT KGLKVYAETC PQYALLSDAI TRCHHHGEVE
SYGVGIDLSS ISESPFTNPD DRFIGSKYIC SPPIRPEGTQ KSIWKGMNNG TFTIVGSDHC
SYNYYEKTST ASKHRAFDPE NNKNGEFRYI PNGLPGVCTR MPLLYDYGYL RGNLTSMMKL
VEIQCTNPAK VYGMYPQKGS ILPGVSDADL VIWYPDDSKK EYNSKPKLIT NKLMEHNCDY
TPFEGIEIKN WPRYTIVKGK IVYKEGEILK ENADGKYLKR GKSFMCTPKN EWVTEWRPKY
ES
