MMCR_STRLA
ID MMCR_STRLA Reviewed; 349 AA.
AC Q9X5T6;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Mitomycin biosynthesis 6-O-methyltransferase {ECO:0000305};
DE EC=2.1.1.316 {ECO:0000269|PubMed:17461583};
DE AltName: Full=Mitomycin 7-O-methyltransferase {ECO:0000303|PubMed:17461583};
GN Name=mmcR {ECO:0000303|PubMed:10099135};
OS Streptomyces lavendulae.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1914;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=NRRL 2564;
RX PubMed=10099135; DOI=10.1016/s1074-5521(99)80040-4;
RA Mao Y.Q., Varoglu M., Sherman D.H.;
RT "Molecular characterization and analysis of the biosynthetic gene cluster
RT for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL
RT 2564.";
RL Chem. Biol. 6:251-263(1999).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, DISRUPTION PHENOTYPE, AND SUBSTRATE SPECIFICITY.
RC STRAIN=NRRL 2564;
RX PubMed=17461583; DOI=10.1021/ja0700193;
RA Grueschow S., Chang L.C., Mao Y., Sherman D.H.;
RT "Hydroxyquinone O-methylation in mitomycin biosynthesis.";
RL J. Am. Chem. Soc. 129:6470-6476(2007).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 2-349 IN COMPLEX WITH SUBSTRATE
RP AND S-ADENOSYL-L-HOMOCYSTEINE, AND SUBUNIT.
RX PubMed=21538548; DOI=10.1002/prot.23040;
RA Singh S., Chang A., Goff R.D., Bingman C.A., Gruschow S., Sherman D.H.,
RA Phillips G.N., Thorson J.S.;
RT "Structural characterization of the mitomycin 7-O-methyltransferase.";
RL Proteins 79:2181-2188(2011).
CC -!- FUNCTION: Involved in the biosynthesis of the quinone methoxy group
CC present in the mitomycin A and B, which are used as anticancer agents
CC (PubMed:10099135, PubMed:17461583). In vitro, catalyzes the 6-O-
CC methylation of both C9-beta- and C9-alpha-configured 6-
CC hydroxymitomycins via the transfer of the S-methyl group of S-adenosyl-
CC L-methionine (AdoMet) to the 6-demethylmitomycin A and B. It can also
CC use hydroxyquinone as substrate (PubMed:17461583).
CC {ECO:0000269|PubMed:10099135, ECO:0000269|PubMed:17461583}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-demethylmitomycin A + S-adenosyl-L-methionine = mitomycin A
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:45104, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:84589, ChEBI:CHEBI:84955;
CC EC=2.1.1.316; Evidence={ECO:0000269|PubMed:17461583};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-demethylmitomycin B + S-adenosyl-L-methionine = mitomycin B
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:45100, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:84590, ChEBI:CHEBI:84952;
CC EC=2.1.1.316; Evidence={ECO:0000269|PubMed:17461583};
CC -!- ACTIVITY REGULATION: Completely inhibited by Zn(2+) and Cu(2+).
CC {ECO:0000269|PubMed:17461583}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.8 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:17461583};
CC KM=170 uM for 6-demethylmitomycin A {ECO:0000269|PubMed:17461583};
CC Note=kcat is 0.110 min(-1) for methyltransferase activity with S-
CC adenosyl-L-methionine as substrate. kcat is 0.103 min(-1) for
CC methyltransferase activity with 6-demethylmitomycin A as substrate.
CC {ECO:0000269|PubMed:17461583};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21538548}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to produce
CC mitomycins A and B, and accumulate 6-demethylmitomycin A and 6-
CC demethylmitomycin B. {ECO:0000269|PubMed:17461583}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family. COMT
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR EMBL; AF127374; AAD32742.2; -; Genomic_DNA.
DR PDB; 3GWZ; X-ray; 1.91 A; A/B/C/D=2-349.
DR PDB; 3GXO; X-ray; 2.30 A; A/B/C/D=2-349.
DR PDBsum; 3GWZ; -.
DR PDBsum; 3GXO; -.
DR AlphaFoldDB; Q9X5T6; -.
DR SMR; Q9X5T6; -.
DR KEGG; ag:AAD32742; -.
DR BioCyc; MetaCyc:MON-20764; -.
DR BRENDA; 2.1.1.316; 133.
DR EvolutionaryTrace; Q9X5T6; -.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008171; F:O-methyltransferase activity; IDA:CACAO.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1901663; P:quinone biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..349
FT /note="Mitomycin biosynthesis 6-O-methyltransferase"
FT /id="PRO_0000435507"
FT ACT_SITE 259
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:21538548"
FT BINDING 167
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21538548"
FT BINDING 190
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21538548"
FT BINDING 213..214
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21538548"
FT BINDING 240..241
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21538548"
FT BINDING 255
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21538548"
FT BINDING 288
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21538548"
FT HELIX 12..41
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 106..115
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 117..124
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 137..141
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 153..177
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:3GWZ"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:3GWZ"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 250..256
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 263..274
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 282..289
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 296..309
FT /evidence="ECO:0007829|PDB:3GWZ"
FT HELIX 316..324
FT /evidence="ECO:0007829|PDB:3GWZ"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 328..335
FT /evidence="ECO:0007829|PDB:3GWZ"
FT STRAND 337..348
FT /evidence="ECO:0007829|PDB:3GWZ"
SQ SEQUENCE 349 AA; 37628 MW; 34F43D4279A60881 CRC64;
MTVEQTPENP GTAARAAAEE TVNDILQGAW KARAIHVAVE LGVPELLQEG PRTATALAEA
TGAHEQTLRR LLRLLATVGV FDDLGHDDLF AQNALSAVLL PDPASPVATD ARFQAAPWHW
RAWEQLTHSV RTGEASFDVA NGTSFWQLTH EDPKARELFN RAMGSVSLTE AGQVAAAYDF
SGAATAVDIG GGRGSLMAAV LDAFPGLRGT LLERPPVAEE ARELLTGRGL ADRCEILPGD
FFETIPDGAD VYLIKHVLHD WDDDDVVRIL RRIATAMKPD SRLLVIDNLI DERPAASTLF
VDLLLLVLVG GAERSESEFA ALLEKSGLRV ERSLPCGAGP VRIVEIRRA
