CINA_CITBR
ID CINA_CITBR Reviewed; 404 AA.
AC Q8VQF6;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=1,8-cineole 2-endo-monooxygenase;
DE EC=1.14.14.133 {ECO:0000269|PubMed:12016226};
DE AltName: Full=cytochrome P450;
DE Short=CYP176A1;
DE Short=P450cin;
GN Name=cinA;
OS Citrobacter braakii.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Citrobacter; Citrobacter freundii complex.
OX NCBI_TaxID=57706;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 171-195, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=12016226; DOI=10.1074/jbc.m203382200;
RA Hawkes D.B., Adams G.W., Burlingame A.L., Ortiz de Montellano P.R.,
RA De Voss J.J.;
RT "Cytochrome P450(cin) (CYP176A), isolation, expression, and
RT characterization.";
RL J. Biol. Chem. 277:27725-27732(2002).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 8-404 IN COMPLEX WITH HEME AND
RP SUBSTRATE, COFACTOR, AND SUBUNIT.
RX PubMed=15260491; DOI=10.1021/bi049293p;
RA Meharenna Y.T., Li H., Hawkes D.B., Pearson A.G., De Voss J., Poulos T.L.;
RT "Crystal structure of P450cin in a complex with its substrate, 1,8-cineole,
RT a close structural homologue to D-camphor, the substrate for P450cam.";
RL Biochemistry 43:9487-9494(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 8-404 OF MUTANT ALA-242 IN
RP COMPLEX WITH HEME AND SUBSTRATE, SUBSTRATE SPECIFICITY, MUTAGENESIS OF
RP ASN-242, AND SUBUNIT.
RX PubMed=18270198; DOI=10.1074/jbc.m709722200;
RA Meharenna Y.T., Slessor K.E., Cavaignac S.M., Poulos T.L., De Voss J.J.;
RT "The critical role of substrate-protein hydrogen bonding in the control of
RT regioselective hydroxylation in p450cin.";
RL J. Biol. Chem. 283:10804-10812(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 8-404 IN COMPLEX WITH HEME AND
RP SUBSTRATE, AND SUBUNIT.
RX PubMed=22775403; DOI=10.1021/bi300666u;
RA Madrona Y., Tripathi S., Li H., Poulos T.L.;
RT "Crystal structures of substrate-free and nitrosyl cytochrome P450cin:
RT implications for O(2) activation.";
RL Biochemistry 51:6623-6631(2012).
CC -!- FUNCTION: Involved in the degradation of cineol (eucalyptol). Catalyzes
CC the initial hydroxylation of cineole exclusively at the pro-R carbon to
CC give the (S)-6beta-hydroxycineole. Cineole is the natural substrate of
CC CinA. {ECO:0000269|PubMed:12016226}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,8-cineole + O2 + reduced [flavodoxin] = 2-endo-hydroxy-1,8-
CC cineole + H(+) + H2O + oxidized [flavodoxin]; Xref=Rhea:RHEA:32899,
CC Rhea:RHEA-COMP:10622, Rhea:RHEA-COMP:10623, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27961,
CC ChEBI:CHEBI:35811, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.133; Evidence={ECO:0000269|PubMed:12016226};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:15260491};
CC -!- PATHWAY: Terpene metabolism; 1,8-cineol degradation.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15260491,
CC ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403}.
CC -!- MISCELLANEOUS: It lacks the conserved threonine believed to be involved
CC in dioxygen activation and instead contains an asparagine at position
CC 242. It is the first isolated P450 using the flavoprotein cindoxin
CC (CinC) as its natural redox partner (PubMed:12016226).
CC {ECO:0000305|PubMed:12016226}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF456128; AAL57614.1; -; Genomic_DNA.
DR PDB; 1T2B; X-ray; 1.70 A; A/B=8-404.
DR PDB; 3BDZ; X-ray; 2.00 A; A/B=8-404.
DR PDB; 3BE0; X-ray; 3.05 A; A/B=8-404.
DR PDB; 4FB2; X-ray; 1.37 A; A/B/C/D=8-404.
DR PDB; 4FMX; X-ray; 1.55 A; A/B=8-404.
DR PDB; 4FYZ; X-ray; 2.32 A; A/B=8-404.
DR PDB; 4L6G; X-ray; 1.37 A; A/B=8-404.
DR PDB; 4L77; X-ray; 1.38 A; A/B=8-404.
DR PDB; 4LHT; X-ray; 2.14 A; A/B=8-404.
DR PDBsum; 1T2B; -.
DR PDBsum; 3BDZ; -.
DR PDBsum; 3BE0; -.
DR PDBsum; 4FB2; -.
DR PDBsum; 4FMX; -.
DR PDBsum; 4FYZ; -.
DR PDBsum; 4L6G; -.
DR PDBsum; 4L77; -.
DR PDBsum; 4LHT; -.
DR AlphaFoldDB; Q8VQF6; -.
DR SMR; Q8VQF6; -.
DR PRIDE; Q8VQF6; -.
DR KEGG; ag:AAL57614; -.
DR BioCyc; MetaCyc:MON-17202; -.
DR BRENDA; 1.14.13.156; 6880.
DR BRENDA; 1.14.14.133; 6880.
DR UniPathway; UPA01032; -.
DR EvolutionaryTrace; Q8VQF6; -.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; IDA:UniProtKB.
DR GO; GO:0046232; P:carbazole catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Heme; Iron; Metal-binding;
KW Monooxygenase; Oxidoreductase.
FT CHAIN 1..404
FT /note="1,8-cineole 2-endo-monooxygenase"
FT /id="PRO_0000422738"
FT BINDING 73
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:15260491,
FT ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403"
FT BINDING 98
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:15260491,
FT ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403"
FT BINDING 102
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:15260491,
FT ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403"
FT BINDING 242
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15260491"
FT BINDING 289
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:15260491,
FT ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403"
FT BINDING 345
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:15260491,
FT ECO:0000269|PubMed:18270198, ECO:0000269|PubMed:22775403"
FT BINDING 347
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT SITE 242
FT /note="Controls regioselective substrate oxidation"
FT MUTAGEN 242
FT /note="N->A: Has only a modest effect on monooxygenase
FT activity. The substrate is free to adopt an alternate
FT conformation which places the ethereal oxygen in an optimal
FT position for polar interactions with solvent."
FT /evidence="ECO:0000269|PubMed:18270198"
FT TURN 10..13
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:3BE0"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:4FB2"
FT TURN 89..92
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 97..106
FT /evidence="ECO:0007829|PDB:4FB2"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 118..130
FT /evidence="ECO:0007829|PDB:4FB2"
FT TURN 131..135
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:4FB2"
FT TURN 144..147
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 148..156
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 180..203
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 209..215
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 225..256
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 258..266
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 271..282
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:4FB2"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:4FB2"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:4L77"
FT HELIX 350..367
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:4FB2"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:4FB2"
SQ SEQUENCE 404 AA; 45266 MW; 1EA334C5CF1B8243 CRC64;
MTATVASTSL FTTADHYHTP LGPDGTPHAF FEALRDEAET TPIGWSEAYG GHWVVAGYKE
IQAVIQNTKA FSNKGVTFPR YETGEFELMM AGQDDPVHKK YRQLVAKPFS PEATDLFTEQ
LRQSTNDLID ARIELGEGDA ATWLANEIPA RLTAILLGLP PEDGDTYRRW VWAITHVENP
EEGAEIFAEL VAHARTLIAE RRTNPGNDIM SRVIMSKIDG ESLSEDDLIG FFTILLLGGI
DNTARFLSSV FWRLAWDIEL RRRLIAHPEL IPNAVDELLR FYGPAMVGRL VTQEVTVGDI
TMKPGQTAML WFPIASRDRS AFDSPDNIVI ERTPNRHLSL GHGIHRCLGA HLIRVEARVA
ITEFLKRIPE FSLDPNKECE WLMGQVAGML HVPIIFPKGK RLSE
