ID   FKBM_STRTA              Reviewed;         260 AA.
AC   P74838;
DT   25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   03-AUG-2022, entry version 57.
DE   RecName: Full=31-O-demethyl-FK506 methyltransferase FkbM;
DE            EC=2.1.1.-;
DE   AltName: Full=FKMT;
GN   Name=fkbM;
OS   Streptomyces tacrolimicus.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=330919;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 55098 / MA 6858;
RX   PubMed=8752344; DOI=10.1128/jb.178.17.5243-5248.1996;
RA   Motamedi H., Shafiee A., Cai S.J., Streicher S.L., Arison B.H.,
RA   Miller R.R.;
RT   "Characterization of methyltransferase and hydroxylase genes involved in
RT   the biosynthesis of the immunosuppressants FK506 and FK520.";
RL   J. Bacteriol. 178:5243-5248(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-40, FUNCTION, COFACTOR, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 55098 / MA 6858;
RX   PubMed=7525282; DOI=10.1111/j.1432-1033.1994.00755.x;
RA   Shafiee A., Motamedi H., Chen T.;
RT   "Enzymology of FK-506 biosynthesis. Purification and characterization of
RT   31-O-desmethylFK-506 O:methyltransferase from Streptomyces sp. MA6858.";
RL   Eur. J. Biochem. 225:755-764(1994).
CC   -!- FUNCTION: Involved in the biosynthesis of FK506, which is a macrolide
CC       antibiotic with immunosuppressant activity. Catalyzes the transfer of a
CC       methyl group from S-adenosyl-L-methionine to the 31-O-position of 31-O-
CC       demethyl-FK506. Also catalyzes the methylation of 31-O-
CC       demethylimmunomycin, the C31 transmethylation reaction of 13,31-O-bis-
CC       demethyl-, 15,31-O-bisdemethyl-, 13,15,31-O-trisdemethyl- and 31-O-
CC       19,22-cyclic-hemiketalimmunomycins, which are all structural analogs of
CC       FK506. {ECO:0000269|PubMed:7525282}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:7525282};
CC   -!- ACTIVITY REGULATION: Inhibited by S-adenosylhomocysteine and
CC       sinefungin. {ECO:0000269|PubMed:7525282}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=23 uM for 31-O-demethyl-FK506 (at pH 7.4 and 34 degrees Celsius)
CC         {ECO:0000269|PubMed:7525282};
CC         KM=28 uM for S-adenosyl-L-methionine (at pH 7.4 and 34 degrees
CC         Celsius) {ECO:0000269|PubMed:7525282};
CC         Vmax=2.33 nmol/min/mg enzyme toward 31-O-demethyl-FK506 (at pH 7.4
CC         and 34 degrees Celsius) {ECO:0000269|PubMed:7525282};
CC         Vmax=2.01 nmol/min/mg enzyme toward S-adenosyl-L-methionine (at pH
CC         7.4 and 34 degrees Celsius) {ECO:0000269|PubMed:7525282};
CC       pH dependence:
CC         Optimum pH is 8.5. {ECO:0000269|PubMed:7525282};
CC       Temperature dependence:
CC         Optimum temperature is 34 degrees Celsius.
CC         {ECO:0000269|PubMed:7525282};
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:7525282}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7525282}.
CC   -!- SIMILARITY: Belongs to the FkbM methyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; U65940; AAC44360.1; -; Genomic_DNA.
DR   AlphaFoldDB; P74838; -.
DR   KEGG; ag:AAC44360; -.
DR   BioCyc; MetaCyc:MON-13930; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR006342; FkbM_mtfrase.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF05050; Methyltransf_21; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   TIGRFAMs; TIGR01444; fkbM_fam; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Magnesium; Methyltransferase;
KW   Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:7525282"
FT   CHAIN           2..260
FT                   /note="31-O-demethyl-FK506 methyltransferase FkbM"
FT                   /id="PRO_0000415368"
SQ   SEQUENCE   260 AA;  28213 MW;  F7F129736351B36C CRC64;
     MSDVVETLRL PNGATVAHVN AGEAQFLYRE IFTDRCYLRH GVELRPGDVV FDVGANIGMF
     MLFAHLEHPG VTVHAFEPAP VPFAALRANA VRHRVAGRVD QCAVSDEAGV RRMTFYPDAT
     LMSGFHPDAA ARKELLRTLG LNGGYTAEDV DMMLAQLPDT GEEIETSVVR LSDVIAERGI
     AAIGLLKIDV EKSERRVLAG VEDADWPRIR QVVAEVHDVD GALGEVVALL RGHGFTVVAE
     QDPLFAGTEI HQVAARRTAG