ID AOTC_XANCP Reviewed; 339 AA.
AC Q8P8J2;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 137.
DE RecName: Full=N-acetylornithine carbamoyltransferase {ECO:0000305|PubMed:16585758};
DE EC=2.1.3.9 {ECO:0000269|PubMed:16585758};
DE AltName: Full=N-acetyl-L-ornithine transcarbamylase {ECO:0000303|PubMed:16585758};
DE Short=AOTCase {ECO:0000303|PubMed:16585758};
DE Short=Acetylornithine transcarbamylase {ECO:0000303|PubMed:16585758};
GN Name=argF' {ECO:0000303|PubMed:15731101, ECO:0000303|PubMed:16585758};
GN OrderedLocusNames=XCC2249;
OS Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB
OS 528 / LMG 568 / P 25).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Xanthomonadales;
OC Xanthomonadaceae; Xanthomonas.
OX NCBI_TaxID=190485;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25;
RX PubMed=12024217; DOI=10.1038/417459a;
RA da Silva A.C.R., Ferro J.A., Reinach F.C., Farah C.S., Furlan L.R.,
RA Quaggio R.B., Monteiro-Vitorello C.B., Van Sluys M.A., Almeida N.F. Jr.,
RA Alves L.M.C., do Amaral A.M., Bertolini M.C., Camargo L.E.A., Camarotte G.,
RA Cannavan F., Cardozo J., Chambergo F., Ciapina L.P., Cicarelli R.M.B.,
RA Coutinho L.L., Cursino-Santos J.R., El-Dorry H., Faria J.B.,
RA Ferreira A.J.S., Ferreira R.C.C., Ferro M.I.T., Formighieri E.F.,
RA Franco M.C., Greggio C.C., Gruber A., Katsuyama A.M., Kishi L.T.,
RA Leite R.P., Lemos E.G.M., Lemos M.V.F., Locali E.C., Machado M.A.,
RA Madeira A.M.B.N., Martinez-Rossi N.M., Martins E.C., Meidanis J.,
RA Menck C.F.M., Miyaki C.Y., Moon D.H., Moreira L.M., Novo M.T.M.,
RA Okura V.K., Oliveira M.C., Oliveira V.R., Pereira H.A., Rossi A.,
RA Sena J.A.D., Silva C., de Souza R.F., Spinola L.A.F., Takita M.A.,
RA Tamura R.E., Teixeira E.C., Tezza R.I.D., Trindade dos Santos M.,
RA Truffi D., Tsai S.M., White F.F., Setubal J.C., Kitajima J.P.;
RT "Comparison of the genomes of two Xanthomonas pathogens with differing host
RT specificities.";
RL Nature 417:459-463(2002).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, PATHWAY, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25;
RX PubMed=16585758; DOI=10.1128/jb.188.8.2974-2982.2006;
RA Morizono H., Cabrera-Luque J., Shi D., Gallegos R., Yamaguchi S., Yu X.,
RA Allewell N.M., Malamy M.H., Tuchman M.;
RT "Acetylornithine transcarbamylase: a novel enzyme in arginine
RT biosynthesis.";
RL J. Bacteriol. 188:2974-2982(2006).
RN [3] {ECO:0007744|PDB:3KZC, ECO:0007744|PDB:3KZK}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF APOENZYME AND COMPLEX WITH
RP N-ACETYLCITRULLINE, AND SUBUNIT.
RC STRAIN=ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25;
RX PubMed=15731101; DOI=10.1074/jbc.c500005200;
RA Shi D., Morizono H., Yu X., Roth L., Caldovic L., Allewell N.M.,
RA Malamy M.H., Tuchman M.;
RT "Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas
RT campestris: a novel enzyme in a new arginine biosynthetic pathway found in
RT several eubacteria.";
RL J. Biol. Chem. 280:14366-14369(2005).
RN [4] {ECO:0007744|PDB:3KZM, ECO:0007744|PDB:3KZN, ECO:0007744|PDB:3KZO}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEXES WITH
RP N(2)-ACETYL-L-ORNITHINE; N-ACETYL-L-NORVALINE AND CARBAMOYL PHOSPHATE, AND
RP SUBUNIT.
RC STRAIN=ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25;
RX PubMed=16741992; DOI=10.1002/prot.21013;
RA Shi D., Yu X., Roth L., Morizono H., Tuchman M., Allewell N.M.;
RT "Structures of N-acetylornithine transcarbamoylase from Xanthomonas
RT campestris complexed with substrates and substrate analogs imply mechanisms
RT for substrate binding and catalysis.";
RL Proteins 64:532-542(2006).
RN [5] {ECO:0007744|PDB:3L02, ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05, ECO:0007744|PDB:3L06}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANTS ALA-92; PRO-92; SER-92
RP AND VAL-92 IN COMPLEXES WITH N-SUCCINYLNORVALINE AND CARBAMOYL PHOSPHATE,
RP AND MUTAGENESIS OF GLU-92.
RX PubMed=17600144; DOI=10.1110/ps.072919907;
RA Shi D., Yu X., Cabrera-Luque J., Chen T.Y., Roth L., Morizono H.,
RA Allewell N.M., Tuchman M.;
RT "A single mutation in the active site swaps the substrate specificity of N-
RT acetyl-L-ornithine transcarbamylase and N-succinyl-L-ornithine
RT transcarbamylase.";
RL Protein Sci. 16:1689-1699(2007).
RN [6] {ECO:0007744|PDB:3M4J, ECO:0007744|PDB:3M4N, ECO:0007744|PDB:3M5C, ECO:0007744|PDB:3M5D}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF WILD-TYPE AND MUTANTS ALA-302;
RP GLU-302 AND ARG-302 IN COMPLEX WITH THE BISUBSTRATE ANALOG
RP N(DELTA)-PHOSPHONOACETYL-N(ALPHA)-ACETYL-L-ORNITHINE (PALAO), CARBOXYLATION
RP AT LYS-302, MUTAGENESIS OF LYS-302, AND ACTIVITY REGULATION.
RX PubMed=20695527; DOI=10.1021/bi1007386;
RA Li Y., Yu X., Ho J., Fushman D., Allewell N.M., Tuchman M., Shi D.;
RT "Reversible post-translational carboxylation modulates the enzymatic
RT activity of N-acetyl-L-ornithine transcarbamylase.";
RL Biochemistry 49:6887-6895(2010).
CC -!- FUNCTION: Catalyzes the transfer of the carbamoyl group from carbamoyl
CC phosphate to the delta-amino group of N(2)-acetyl-L-ornithine to
CC produce N(2)-acetyl-L-citrulline. This is a step in an alternative
CC arginine biosynthesis pathway. The enzyme has no activity with
CC ornithine. {ECO:0000269|PubMed:16585758}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl phosphate + N(2)-acetyl-L-ornithine = H(+) + N(2)-
CC acetyl-L-citrulline + phosphate; Xref=Rhea:RHEA:18609,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57805,
CC ChEBI:CHEBI:58228, ChEBI:CHEBI:58765; EC=2.1.3.9;
CC Evidence={ECO:0000269|PubMed:16585758};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18610;
CC Evidence={ECO:0000305|PubMed:16585758};
CC -!- ACTIVITY REGULATION: Carboxylation at Lys-302 increases the catalytic
CC activity of the enzyme (PubMed:20695527). Is potently inhibited by
CC N(alpha)-acetyl-N(delta)-phosphonoacetyl-L-ornithine (PALAO)
CC (PubMed:16585758). {ECO:0000269|PubMed:16585758,
CC ECO:0000269|PubMed:20695527}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.01 mM for carbamoyl phosphate {ECO:0000269|PubMed:16585758};
CC KM=1.05 mM for N(2)-acetyl-L-ornithine {ECO:0000269|PubMed:16585758};
CC Vmax=65.28 umol/min/mg enzyme towards N(2)-acetyl-L-ornithine
CC {ECO:0000269|PubMed:16585758};
CC Vmax=50.68 umol/min/mg enzyme towards carbamoyl phosphate
CC {ECO:0000269|PubMed:16585758};
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis.
CC {ECO:0000305|PubMed:16585758}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:15731101,
CC ECO:0000269|PubMed:16741992}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the aspartate/ornithine carbamoyltransferase
CC superfamily. AOTCase family. {ECO:0000255|HAMAP-Rule:MF_02234,
CC ECO:0000305}.
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DR EMBL; AE008922; AAM41528.1; -; Genomic_DNA.
DR RefSeq; NP_637604.1; NC_003902.1.
DR RefSeq; WP_011037393.1; NC_003902.1.
DR PDB; 3KZC; X-ray; 2.20 A; A=1-339.
DR PDB; 3KZK; X-ray; 1.90 A; A=1-339.
DR PDB; 3KZM; X-ray; 1.95 A; A=1-339.
DR PDB; 3KZN; X-ray; 1.80 A; A=1-339.
DR PDB; 3KZO; X-ray; 1.90 A; A=1-339.
DR PDB; 3L02; X-ray; 2.30 A; A=1-339.
DR PDB; 3L04; X-ray; 2.50 A; A=1-339.
DR PDB; 3L05; X-ray; 2.80 A; A=1-339.
DR PDB; 3L06; X-ray; 2.81 A; A=1-339.
DR PDB; 3M4J; X-ray; 2.20 A; A=1-339.
DR PDB; 3M4N; X-ray; 1.90 A; A=1-339.
DR PDB; 3M5C; X-ray; 1.85 A; A=1-339.
DR PDB; 3M5D; X-ray; 2.20 A; A=1-339.
DR PDBsum; 3KZC; -.
DR PDBsum; 3KZK; -.
DR PDBsum; 3KZM; -.
DR PDBsum; 3KZN; -.
DR PDBsum; 3KZO; -.
DR PDBsum; 3L02; -.
DR PDBsum; 3L04; -.
DR PDBsum; 3L05; -.
DR PDBsum; 3L06; -.
DR PDBsum; 3M4J; -.
DR PDBsum; 3M4N; -.
DR PDBsum; 3M5C; -.
DR PDBsum; 3M5D; -.
DR AlphaFoldDB; Q8P8J2; -.
DR SMR; Q8P8J2; -.
DR STRING; 190485.XCC2249; -.
DR DrugBank; DB08554; N-(3-carboxypropanoyl)-L-norvaline.
DR DrugBank; DB02368; N-Acetyl-L-Citrulline.
DR EnsemblBacteria; AAM41528; AAM41528; XCC2249.
DR KEGG; xcc:XCC2249; -.
DR PATRIC; fig|190485.4.peg.2399; -.
DR eggNOG; COG0078; Bacteria.
DR HOGENOM; CLU_043846_3_3_6; -.
DR OrthoDB; 9802587at2; -.
DR BioCyc; MetaCyc:MONOMER-12073; -.
DR BRENDA; 2.1.3.9; 6708.
DR UniPathway; UPA00068; -.
DR EvolutionaryTrace; Q8P8J2; -.
DR Proteomes; UP000001010; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016597; F:amino acid binding; IEA:InterPro.
DR GO; GO:0043857; F:N-acetylornithine carbamoyltransferase activity; IDA:CACAO.
DR GO; GO:0004585; F:ornithine carbamoyltransferase activity; IBA:GO_Central.
DR GO; GO:0042450; P:arginine biosynthetic process via ornithine; IBA:GO_Central.
DR GO; GO:0019240; P:citrulline biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.1370; Aspartate/ornithine carbamoyltransferase; 2.
DR HAMAP; MF_02234; AOTCase; 1.
DR InterPro; IPR043695; ArgF.
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 PANTHER; PTHR45753; ORNITHINE CARBAMOYLTRANSFERASE, MITOCHONDRIAL; 1.
DR PANTHER; PTHR45753:SF3; ORNITHINE TRANSCARBAMYLASE, MITOCHONDRIAL; 1.
DR Pfam; PF00185; OTCace; 1.
DR Pfam; PF02729; OTCace_N; 1.
DR PRINTS; PR00100; AOTCASE.
DR PRINTS; PR00101; ATCASE.
DR SUPFAM; SSF53671; Aspartate/ornithine carbamoyltransferase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Arginine biosynthesis; Cytoplasm;
KW Reference proteome; Transferase.
FT CHAIN 1..339
FT /note="N-acetylornithine carbamoyltransferase"
FT /id="PRO_0000113268"
FT BINDING 49..52
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT BINDING 77
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT BINDING 112
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT BINDING 144
FT /ligand="N(2)-acetyl-L-ornithine"
FT /ligand_id="ChEBI:CHEBI:57805"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0007744|PDB:3KZN"
FT BINDING 148..151
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT BINDING 252
FT /ligand="N(2)-acetyl-L-ornithine"
FT /ligand_id="ChEBI:CHEBI:57805"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0007744|PDB:3KZN"
FT BINDING 294..295
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT BINDING 295
FT /ligand="N(2)-acetyl-L-ornithine"
FT /ligand_id="ChEBI:CHEBI:57805"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0007744|PDB:3KZN"
FT BINDING 322
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:16741992,
FT ECO:0000269|PubMed:17600144, ECO:0007744|PDB:3KZM,
FT ECO:0007744|PDB:3KZO, ECO:0007744|PDB:3L02,
FT ECO:0007744|PDB:3L04, ECO:0007744|PDB:3L05,
FT ECO:0007744|PDB:3L06"
FT SITE 92
FT /note="Key residue in conferring substrate specificity for
FT N-acetyl-L-ornithine versus N-succinyl-L-ornithine"
FT /evidence="ECO:0000269|PubMed:17600144"
FT MOD_RES 302
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000269|PubMed:20695527"
FT MUTAGEN 92
FT /note="E->A,P,S,V: Generates an enzyme capable of
FT carbamoylation of N-succinyl-L-ornithine while losing its
FT ability to use N-acetyl-L-ornithine as substrate, thus
FT converting it from a N-acetylornithine transcarbamylase
FT (AOTCase) to a N-succinylornithine transcarbamylase
FT (SOTCase)."
FT /evidence="ECO:0000269|PubMed:17600144"
FT MUTAGEN 302
FT /note="K->A,E,R: Significant decrease in enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:20695527"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 14..29
FT /evidence="ECO:0007829|PDB:3KZN"
FT TURN 35..38
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 50..62
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:3KZN"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:3KZK"
FT HELIX 127..135
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 149..163
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 187..198
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 216..229
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 239..243
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 266..270
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 271..276
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:3KZN"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:3KZN"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:3KZN"
FT HELIX 315..333
FT /evidence="ECO:0007829|PDB:3KZN"
SQ SEQUENCE 339 AA; 37873 MW; 8FEFBA16773A00D5 CRC64;
MSLKHFLNTQ DWSRAELDAL LTQAALFKRN KLGSELKGKS IALVFFNPSM RTRTSFELGA
FQLGGHAVVL QPGKDAWPIE FNLGTVMDGD TEEHIAEVAR VLGRYVDLIG VRAFPKFVDW
SKDREDQVLK SFAKYSPVPV INMETITHPC QELAHALALQ EHFGTPDLRG KKYVLTWTYH
PKPLNTAVAN SALTIATRMG MDVTLLCPTP DYILDERYMD WAAQNVAESG GSLQVSHDID
SAYAGADVVY AKSWGALPFF GNWEPEKPIR DQYQHFIVDE RKMALTNNGV FSHCLPLRRN
VKATDAVMDS PNCIAIDEAE NRLHVQKAIM AALVGQSRP
//
