OTCA_PYRFU
ID OTCA_PYRFU Reviewed; 315 AA.
AC Q51742;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 6.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Ornithine carbamoyltransferase, anabolic {ECO:0000303|PubMed:9288929};
DE Short=OTCase {ECO:0000303|PubMed:9288929};
DE EC=2.1.3.3 {ECO:0000255|HAMAP-Rule:MF_01109};
GN Name=argF {ECO:0000303|PubMed:9288929}; OrderedLocusNames=PF0594;
OS Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=186497;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=9288929; DOI=10.1111/j.1432-1033.1997.01038.x;
RA Roovers M., Hetcke C., Legrain C., Thomm M., Glansdorff N.;
RT "Isolation of the gene encoding Pyrococcus furiosus ornithine
RT carbamoyltransferase and study of its expression profile in vivo and in
RT vitro.";
RL Eur. J. Biochem. 247:1038-1045(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA DiRuggiero J., Robb F.T.;
RT "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT horikoshii inferred from complete genomic sequences.";
RL Genetics 152:1299-1305(1999).
RN [3]
RP PROTEIN SEQUENCE OF 2-12, FUNCTION AS AN OTCASE, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=9288930; DOI=10.1111/j.1432-1033.1997.01046.x;
RA Legrain C., Villeret V., Roovers M., Gigot D., Dideberg O., Pierard A.,
RA Glansdorff N.;
RT "Biochemical characterisation of ornithine carbamoyltransferase from
RT Pyrococcus furiosus.";
RL Eur. J. Biochem. 247:1046-1055(1997).
RN [4]
RP INTERACTION WITH CARBAMOYL-PHOSPHATE SYNTHETASE.
RX PubMed=11893735; DOI=10.1074/jbc.m111481200;
RA Massant J., Verstreken P., Durbecq V., Kholti A., Legrain C., Beeckmans S.,
RA Cornelis P., Glansdorff N.;
RT "Metabolic channeling of carbamoyl phosphate, a thermolabile intermediate:
RT evidence for physical interaction between carbamate kinase-like carbamoyl-
RT phosphate synthetase and ornithine carbamoyltransferase from the
RT hyperthermophile Pyrococcus furiosus.";
RL J. Biol. Chem. 277:18517-18522(2002).
RN [5]
RP MUTAGENESIS OF TYR-228; ALA-241 AND GLU-278.
RX PubMed=11208811; DOI=10.1128/jb.183.3.1101-1105.2001;
RA Roovers M., Sanchez R., Legrain C., Glansdorff N.;
RT "Experimental evolution of enzyme temperature activity profile: selection
RT in vivo and characterization of low-temperature-adapted mutants of
RT Pyrococcus furiosus ornithine carbamoyltransferase.";
RL J. Bacteriol. 183:1101-1105(2001).
RN [6]
RP MUTAGENESIS OF TRP-22; GLU-26; MET-30 AND TRP-34.
RX PubMed=11453986; DOI=10.1046/j.1432-1327.2001.02302.x;
RA Clantin B., Tricot C., Lonhienne T., Stalon V., Villeret V.;
RT "Probing the role of oligomerization in the high thermal stability of
RT Pyrococcus furiosus ornithine carbamoyltransferase by site-specific
RT mutants.";
RL Eur. J. Biochem. 268:3937-3942(2001).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), BIOPHYSICOCHEMICAL PROPERTIES,
RP DOMAIN, AND SUBUNIT.
RX PubMed=9501170; DOI=10.1073/pnas.95.6.2801;
RA Villeret V., Clantin B., Tricot C., Legrain C., Roovers M., Stalon V.,
RA Glansdorff N., van Beeumen J.;
RT "The crystal structure of Pyrococcus furiosus ornithine
RT carbamoyltransferase reveals a key role for oligomerization in enzyme
RT stability at extremely high temperatures.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2801-2806(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS)IN COMPLEX WITH SUBSTRATE ANALOG,
RP THERMOSTABILITY, AND SUBUNIT.
RX PubMed=14646072; DOI=10.1107/s0907444903019231;
RA Massant J., Wouters J., Glansdorff N.;
RT "Refined structure of Pyrococcus furiosus ornithine carbamoyltransferase at
RT 1.87 A.";
RL Acta Crystallogr. D 59:2140-2149(2003).
CC -!- FUNCTION: Reversibly catalyzes the transfer of the carbamoyl group from
CC carbamoyl phosphate (CP) to the N(epsilon) atom of ornithine (ORN) to
CC produce L-citrulline, which is a substrate for argininosuccinate
CC synthetase, the enzyme involved in the final step in arginine
CC biosynthesis. {ECO:0000269|PubMed:9288930}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl phosphate + L-ornithine = H(+) + L-citrulline +
CC phosphate; Xref=Rhea:RHEA:19513, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:46911, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:58228; EC=2.1.3.3; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01109};
CC -!- ACTIVITY REGULATION: Inhibited by the bisubstrate delta-N-
CC phosphonoacetyl-L-ornithine (PALO). {ECO:0000269|PubMed:9288930}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 mM for L-ornithine {ECO:0000269|PubMed:9288930};
CC KM=0.13 mM for carbamoyl phosphate {ECO:0000269|PubMed:9288930};
CC pH dependence:
CC Optimum pH is 6.5 (at 55 degrees Celsius).
CC {ECO:0000269|PubMed:9288930, ECO:0000269|PubMed:9501170};
CC Temperature dependence:
CC Extreme thermal stability. It maintains about 50% of its activity
CC after heat treatment for 60 min at 100 degrees Celsius.
CC {ECO:0000269|PubMed:9501170};
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC from L-ornithine and carbamoyl phosphate: step 1/3. {ECO:0000255|HAMAP-
CC Rule:MF_01109}.
CC -!- SUBUNIT: Homododecamer (tetramer of trimers).
CC {ECO:0000269|PubMed:9501170, ECO:0000305|PubMed:14646072}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: The monomer folds into two domains of similar size. The N-
CC terminal domain is the carbamoylphosphate-binding domain; ornithine
CC binds to the C-terminal domain. {ECO:0000269|PubMed:9501170}.
CC -!- MISCELLANEOUS: It interacts physically with carbamoyl-phosphate
CC synthetase (CKase), forming a channeling cluster for carbamoyl
CC phosphate. This prevents the thermodenaturation of carbamoyl phosphate,
CC an extremely thermolabile and potentially toxic metabolic intermediate
CC (PubMed:9501170). {ECO:0000305|PubMed:9501170}.
CC -!- SIMILARITY: Belongs to the aspartate/ornithine carbamoyltransferase
CC superfamily. OTCase family. {ECO:0000305}.
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DR EMBL; X99225; CAA67609.1; -; Genomic_DNA.
DR EMBL; Y12727; CAA73260.1; -; Genomic_DNA.
DR EMBL; AE009950; AAL80718.1; -; Genomic_DNA.
DR PIR; T45077; T45077.
DR RefSeq; WP_011011713.1; NZ_CP023154.1.
DR PDB; 1A1S; X-ray; 2.70 A; A=2-315.
DR PDB; 1PVV; X-ray; 1.87 A; A=1-315.
DR PDBsum; 1A1S; -.
DR PDBsum; 1PVV; -.
DR AlphaFoldDB; Q51742; -.
DR SMR; Q51742; -.
DR DIP; DIP-48301N; -.
DR IntAct; Q51742; 1.
DR STRING; 186497.PF0594; -.
DR PRIDE; Q51742; -.
DR EnsemblBacteria; AAL80718; AAL80718; PF0594.
DR GeneID; 41712399; -.
DR KEGG; pfu:PF0594; -.
DR PATRIC; fig|186497.12.peg.623; -.
DR eggNOG; arCOG00912; Archaea.
DR HOGENOM; CLU_043846_3_2_2; -.
DR OMA; DGNNVCN; -.
DR OrthoDB; 43727at2157; -.
DR PhylomeDB; Q51742; -.
DR BRENDA; 2.1.3.3; 5243.
DR UniPathway; UPA00068; UER00112.
DR EvolutionaryTrace; Q51742; -.
DR Proteomes; UP000001013; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016597; F:amino acid binding; IEA:InterPro.
DR GO; GO:0004585; F:ornithine carbamoyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006526; P:arginine biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.1370; -; 2.
DR HAMAP; MF_01109; OTCase; 1.
DR InterPro; IPR006132; Asp/Orn_carbamoyltranf_P-bd.
DR InterPro; IPR006130; Asp/Orn_carbamoylTrfase.
DR InterPro; IPR036901; Asp/Orn_carbamoylTrfase_sf.
DR InterPro; IPR006131; Asp_carbamoyltransf_Asp/Orn-bd.
DR InterPro; IPR002292; Orn/put_carbamltrans.
DR InterPro; IPR024904; OTCase_ArgI.
DR Pfam; PF00185; OTCace; 1.
DR Pfam; PF02729; OTCace_N; 1.
DR PRINTS; PR00100; AOTCASE.
DR PRINTS; PR00102; OTCASE.
DR SUPFAM; SSF53671; SSF53671; 1.
DR TIGRFAMs; TIGR00658; orni_carb_tr; 1.
DR PROSITE; PS00097; CARBAMOYLTRANSFERASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Arginine biosynthesis; Cytoplasm;
KW Direct protein sequencing; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9288930"
FT CHAIN 2..315
FT /note="Ornithine carbamoyltransferase, anabolic"
FT /id="PRO_0000113073"
FT BINDING 57..60
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 84
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000305|PubMed:14646072"
FT BINDING 108
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 135..138
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 166
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 230
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 234..235
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 270..271
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT BINDING 298
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01109"
FT MUTAGEN 22
FT /note="W->A: Decreased heat stability."
FT /evidence="ECO:0000269|PubMed:11453986"
FT MUTAGEN 26
FT /note="E->Q: Increased dissociation of dodecamers into
FT trimers."
FT /evidence="ECO:0000269|PubMed:11453986"
FT MUTAGEN 30
FT /note="M->A: Increased dissociation of dodecamers into
FT trimers."
FT /evidence="ECO:0000269|PubMed:11453986"
FT MUTAGEN 34
FT /note="W->A: Increased dissociation of dodecamers into
FT trimers."
FT /evidence="ECO:0000269|PubMed:11453986"
FT MUTAGEN 228
FT /note="Y->C: Becomes active at low temperatures; when
FT associated with G-278."
FT /evidence="ECO:0000269|PubMed:11208811"
FT MUTAGEN 241
FT /note="A->D: Becomes active at low temperatures; when
FT associated with G-278."
FT /evidence="ECO:0000269|PubMed:11208811"
FT MUTAGEN 278
FT /note="E->G: Becomes active at low temperatures; when
FT associated with C-228 or D-241."
FT /evidence="ECO:0000269|PubMed:11208811"
FT CONFLICT 206
FT /note="E -> ER (in Ref. 1; CAA73260)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="Missing (in Ref. 1; CAA67609)"
FT /evidence="ECO:0000305"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 18..37
FT /evidence="ECO:0007829|PDB:1PVV"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:1PVV"
FT TURN 84..88
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:1PVV"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 136..150
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 166..177
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 194..207
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:1PVV"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 255..259
FT /evidence="ECO:0007829|PDB:1PVV"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:1PVV"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:1PVV"
FT HELIX 291..311
FT /evidence="ECO:0007829|PDB:1PVV"
SQ SEQUENCE 315 AA; 35181 MW; 14404FBDC2ECCB95 CRC64;
MVVSLAGRDL LCLQDYTAEE IWTILETAKM FKIWQKIGKP HRLLEGKTLA MIFQKPSTRT
RVSFEVAMAH LGGHALYLNA QDLQLRRGET IADTARVLSR YVDAIMARVY DHKDVEDLAK
YATVPVINGL SDFSHPCQAL ADYMTIWEKK GTIKGVKVVY VGDGNNVAHS LMIAGTKLGA
DVVVATPEGY EPDEKVIKWA EQNAAESGGS FELLHDPVKA VKDADVIYTD VWASMGQEAE
AEERRKIFRP FQVNKDLVKH AKPDYMFMHC LPAHRGEEVT DDVIDSPNSV VWDQAENRLH
AQKAVLALVM GGIKF
