FLA_STRCT
ID FLA_STRCT Reviewed; 299 AA.
AC Q70GK9;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=5'-fluoro-5'-deoxy-adenosine synthase {ECO:0000303|PubMed:14765200};
DE Short=5'-FDAS {ECO:0000303|PubMed:14765200};
DE EC=2.5.1.63 {ECO:0000269|PubMed:12860396, ECO:0000269|PubMed:14765200, ECO:0000269|PubMed:17985882};
DE AltName: Full=5'-fluorodeoxyadenosine synthase {ECO:0000303|PubMed:12860396};
DE AltName: Full=Fluorinase {ECO:0000303|PubMed:16370017};
GN Name=flA {ECO:0000303|PubMed:14765200};
OS Streptomyces cattleya.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=29303;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN
RP COMPLEX WITH SUBSTRATES, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=14765200; DOI=10.1038/nature02280;
RA Dong C., Huang F., Deng H., Schaffrath C., Spencer J.B., O'Hagan D.,
RA Naismith J.H.;
RT "Crystal structure and mechanism of a bacterial fluorinating enzyme.";
RL Nature 427:561-565(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16720268; DOI=10.1016/j.chembiol.2006.02.014;
RA Huang F., Haydock S.F., Spiteller D., Mironenko T., Li T.-L., O'Hagan D.,
RA Leadlay P.F., Spencer J.B.;
RT "The gene cluster for fluorometabolite biosynthesis in Streptomyces
RT cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A.";
RL Chem. Biol. 13:475-484(2006).
RN [3]
RP PROTEIN SEQUENCE OF 2-25, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND MASS SPECTROMETRY.
RX PubMed=12860396; DOI=10.1016/s0014-5793(03)00688-4;
RA Schaffrath C., Deng H., O'Hagan D.;
RT "Isolation and characterisation of 5'-fluorodeoxyadenosine synthase, a
RT fluorination enzyme from Streptomyces cattleya.";
RL FEBS Lett. 547:111-114(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP AND SUBUNIT.
RA Mcewan A.R., Deng H., Mcglinchey R.P., Robinson D.R., O'Hagan D.,
RA Naismith J.H.;
RT "Substrates and inhibitors of the fluorinase from Streptomyces cattleya.";
RL Submitted (OCT-2005) to the PDB data bank.
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP FUNCTION, AND SUBUNIT.
RX PubMed=16370017; DOI=10.1002/anie.200503582;
RA Deng H., Cobb S.L., McEwan A.R., McGlinchey R.P., Naismith J.H.,
RA O'Hagan D., Robinson D.A., Spencer J.B.;
RT "The fluorinase from Streptomyces cattleya is also a chlorinase.";
RL Angew. Chem. Int. Ed. 45:759-762(2006).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS)IN COMPLEX WITH SUBSTRATE ANALOGS,
RP FUNCTION, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RX PubMed=16604208; DOI=10.1039/b600574h;
RA Cobb S.L., Deng H., McEwan A.R., Naismith J.H., O'Hagan D., Robinson D.A.;
RT "Substrate specificity in enzymatic fluorination. The fluorinase from
RT Streptomyces cattleya accepts 2'-deoxyadenosine substrates.";
RL Org. Biomol. Chem. 4:1458-1460(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH SAM AND SUBSTRATE
RP ANALOGS, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-16; THR-80;
RP PHE-156 AND SER-158, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=17985882; DOI=10.1021/ja0731569;
RA Zhu X., Robinson D.A., McEwan A.R., O'Hagan D., Naismith J.H.;
RT "Mechanism of enzymatic fluorination in Streptomyces cattleya.";
RL J. Am. Chem. Soc. 129:14597-14604(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS,
RP AND SUBUNIT.
RA Thomson S., Mcmahon S.A., Naismith J.H., O'Hagan D.;
RT "Structure of a bacterial fluorinating enzyme with.";
RL Submitted (FEB-2014) to the PDB data bank.
CC -!- FUNCTION: Involved in the biosynthesis of fluorometabolites. Catalyzes
CC the formation of a C-F bond by combining S-adenosyl-L-methionine (SAM)
CC and fluoride to generate 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-
CC methionine. It can also use 2'-deoxyadenosine in place of adenosine as
CC substrate. {ECO:0000269|PubMed:12860396, ECO:0000269|PubMed:14765200,
CC ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
CC ECO:0000269|PubMed:16720268, ECO:0000269|PubMed:17985882}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fluoride + S-adenosyl-L-methionine = 5'-deoxy-5'-
CC fluoroadenosine + L-methionine; Xref=Rhea:RHEA:16661,
CC ChEBI:CHEBI:12060, ChEBI:CHEBI:17051, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:59789; EC=2.5.1.63;
CC Evidence={ECO:0000269|PubMed:12860396, ECO:0000269|PubMed:14765200,
CC ECO:0000269|PubMed:17985882};
CC -!- ACTIVITY REGULATION: Competitively inhibited by S-adenosyl-L-
CC homocysteine (AdoHcy) and S-adenosyl-L-homocysteine (SAH). Sinefungin
CC is only weakly inhibitory. {ECO:0000269|PubMed:16720268}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.5 uM for SAM (at pH 7.8 and degrees Celsius)
CC {ECO:0000269|PubMed:17985882};
CC KM=74 uM for SAM (at pH 7.9 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:14765200};
CC KM=0.42 mM for SAM (at pH 7.8 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:12860396};
CC KM=2 mM for fluoride (at pH 7.9 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:14765200};
CC KM=8.56 mM for fluoride (at pH 7.8 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:12860396};
CC KM=10.2 mM for fluoride (at pH 7.8 and degrees Celsius)
CC {ECO:0000269|PubMed:17985882};
CC Vmax=1.28 umol/min/mg enzyme toward SAM (at pH 7.8 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:12860396};
CC Vmax=1.59 umol/min/mg enzyme toward fluoride (at pH 7.8 and 25
CC degrees Celsius) {ECO:0000269|PubMed:12860396};
CC Note=kcat is 0.07 sec(-1) for 5'-FDA synthase activity with SAM as
CC substrate(at pH 7.9 and 37 degrees Celsius). kcat is 0.06 sec(-1) for
CC 5'-FDA synthase activity with fluoride as substrate (at pH 7.9 and 37
CC degrees Celsius). {ECO:0000269|PubMed:14765200,
CC ECO:0000269|PubMed:17985882};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius.
CC {ECO:0000269|PubMed:12860396};
CC -!- SUBUNIT: Homohexamer; dimers of trimer. {ECO:0000269|PubMed:12860396,
CC ECO:0000269|PubMed:14765200, ECO:0000269|PubMed:16370017,
CC ECO:0000269|PubMed:16604208, ECO:0000269|PubMed:17985882,
CC ECO:0000269|Ref.4, ECO:0000269|Ref.8}.
CC -!- MASS SPECTROMETRY: Mass=32200; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12860396};
CC -!- SIMILARITY: Belongs to the SAM hydrolase / SAM-dependent halogenase
CC family. {ECO:0000305}.
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DR EMBL; AJ581748; CAE46446.1; -; Genomic_DNA.
DR EMBL; AM055586; CAJ20006.1; -; Genomic_DNA.
DR PDB; 1RQP; X-ray; 1.80 A; A/B/C=1-299.
DR PDB; 1RQR; X-ray; 2.67 A; A/B/C=1-299.
DR PDB; 2C2W; X-ray; 2.00 A; A/B/C=1-299.
DR PDB; 2C4T; X-ray; 2.30 A; A/B/C=1-299.
DR PDB; 2C4U; X-ray; 2.50 A; A/B/C/D/E/F=1-299.
DR PDB; 2C5B; X-ray; 2.50 A; A/B/C=1-299.
DR PDB; 2C5H; X-ray; 2.70 A; A/B/C=1-299.
DR PDB; 2CBX; X-ray; 2.00 A; A/B/C=1-299.
DR PDB; 2CC2; X-ray; 2.00 A; A/B/C=1-299.
DR PDB; 2V7T; X-ray; 2.15 A; A/B/C=1-299.
DR PDB; 2V7U; X-ray; 2.00 A; A/B/C=1-299.
DR PDB; 2V7V; X-ray; 1.94 A; A/B/C=1-299.
DR PDB; 2V7W; X-ray; 1.90 A; A/B/C=1-299.
DR PDB; 2V7X; X-ray; 1.96 A; A/B/C=1-299.
DR PDB; 4CQJ; X-ray; 2.44 A; A/B/C=1-299.
DR PDB; 5FIU; X-ray; 1.84 A; A/B/C=1-299.
DR PDBsum; 1RQP; -.
DR PDBsum; 1RQR; -.
DR PDBsum; 2C2W; -.
DR PDBsum; 2C4T; -.
DR PDBsum; 2C4U; -.
DR PDBsum; 2C5B; -.
DR PDBsum; 2C5H; -.
DR PDBsum; 2CBX; -.
DR PDBsum; 2CC2; -.
DR PDBsum; 2V7T; -.
DR PDBsum; 2V7U; -.
DR PDBsum; 2V7V; -.
DR PDBsum; 2V7W; -.
DR PDBsum; 2V7X; -.
DR PDBsum; 4CQJ; -.
DR PDBsum; 5FIU; -.
DR AlphaFoldDB; Q70GK9; -.
DR SMR; Q70GK9; -.
DR DrugBank; DB07170; 5'-FLUORO-2',5'-DIDEOXYADENOSINE.
DR DrugBank; DB03716; 5'-Fluoro-5'-Deoxyadenosine.
DR OMA; EGYVGAM; -.
DR BioCyc; MetaCyc:MON-15922; -.
DR BRENDA; 2.5.1.63; 5990.
DR BRENDA; 2.5.1.94; 5990.
DR SABIO-RK; Q70GK9; -.
DR EvolutionaryTrace; Q70GK9; -.
DR GO; GO:0033846; F:adenosyl-fluoride synthase activity; IEA:UniProtKB-EC.
DR Gene3D; 2.40.30.90; -; 1.
DR Gene3D; 3.40.50.10790; -; 1.
DR InterPro; IPR030978; Fluorinase.
DR InterPro; IPR002747; SAM_Chlor/Fluor.
DR InterPro; IPR023227; SAM_OH_AdoTrfase_C.
DR InterPro; IPR023228; SAM_OH_AdoTrfase_N.
DR PANTHER; PTHR35092; PTHR35092; 2.
DR Pfam; PF01887; SAM_adeno_trans; 2.
DR PIRSF; PIRSF006779; UCP006779; 1.
DR SUPFAM; SSF101852; SSF101852; 1.
DR SUPFAM; SSF102522; SSF102522; 1.
DR TIGRFAMs; TIGR04507; fluorinase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; S-adenosyl-L-methionine;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12860396"
FT CHAIN 2..299
FT /note="5'-fluoro-5'-deoxy-adenosine synthase"
FT /id="PRO_0000430663"
FT BINDING 16
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 21..23
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 77
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 158
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 210
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 215
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 269..270
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT BINDING 277..279
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14765200,
FT ECO:0000269|PubMed:16370017, ECO:0000269|PubMed:16604208,
FT ECO:0000269|PubMed:17985882, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.8"
FT MUTAGEN 16
FT /note="D->A: Loss of 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 16
FT /note="D->N: Loss of 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 16
FT /note="D->S: Loss of 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 80
FT /note="T->A: Weak 5'-FDA synthase activity. 2-fold increase
FT of the affinity binding for S-adenosyl-L-methionine and 4-
FT fold decrease of the affinity binding for fluoride."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 80
FT /note="T->S: The 5'-FDA synthase activity and the affinity
FT binding for S-adenosyl-L-methionine and fuoride are similar
FT to the wild-type."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 156
FT /note="F->A: Weak 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 156
FT /note="F->V: Weak 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 158
FT /note="S->A: The 5'-FDA synthase activity is 40% of the
FT wild-type. 2-fold increase of the affinity binding for
FT fluoride and 1.5-fold decrease of the affinity binding for
FT S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:17985882"
FT MUTAGEN 158
FT /note="S->G: Weak 5'-FDA synthase activity."
FT /evidence="ECO:0000269|PubMed:17985882"
FT STRAND 10..17
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 19..22
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 23..34
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 163..170
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:2C5B"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 211..214
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:1RQP"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 244..253
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 271..277
FT /evidence="ECO:0007829|PDB:1RQP"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:1RQP"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:1RQP"
SQ SEQUENCE 299 AA; 32370 MW; 54697A2F68121731 CRC64;
MAANSTRRPI IAFMSDLGTT DDSVAQCKGL MYSICPDVTV VDVCHSMTPW DVEEGARYIV
DLPRFFPEGT VFATTTYPAT GTTTRSVAVR IKQAAKGGAR GQWAGSGAGF ERAEGSYIYI
APNNGLLTTV LEEHGYLEAY EVTSPKVIPE QPEPTFYSRE MVAIPSAHLA AGFPLSEVGR
PLEDHEIVRF NRPAVEQDGE ALVGVVSAID HPFGNVWTNI HRTDLEKAGI GYGARLRLTL
DGVLPFEAPL TPTFADAGEI GNIAIYLNSR GYLSIARNAA SLAYPYHLKE GMSARVEAR
