AKNK_STRGJ
ID AKNK_STRGJ Reviewed; 440 AA.
AC Q9L555;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Aclacinomycin-T 2-deoxy-L-fucose transferase {ECO:0000303|PubMed:15078101};
DE Short=AknK {ECO:0000303|PubMed:15078101};
DE EC=2.4.1.327 {ECO:0000269|PubMed:15078101};
DE AltName: Full=L-2-deoxyfucosyltransferase {ECO:0000303|PubMed:15078101};
GN Name=aknK {ECO:0000303|PubMed:15078101};
OS Streptomyces galilaeus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=33899;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC31615;
RX PubMed=12137949; DOI=10.1016/s0378-1119(02)00699-6;
RA Raty K., Kantola J., Hautala A., Hakala J., Ylihonko K., Mantsala P.;
RT "Cloning and characterization of Streptomyces galilaeus aclacinomycins
RT polyketide synthase (PKS) cluster.";
RL Gene 293:115-122(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC31615;
RA Niemi J.;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, AND SUBSTRATE
RP SPECIFICITY.
RC STRAIN=ATCC31615;
RX PubMed=15078101; DOI=10.1021/bi035945i;
RA Lu W., Leimkuhler C., Oberthuer M., Kahne D., Walsh C.T.;
RT "AknK is an L-2-deoxyfucosyltransferase in the biosynthesis of the
RT anthracycline aclacinomycin A.";
RL Biochemistry 43:4548-4558(2004).
CC -!- FUNCTION: Involved in the biosynthesis of the trisaccharide moiety
CC characteristic of the antitumor drug aclacinomycins. In the first
CC reaction, AknK catalyzes the transfer of 2-deoxy-beta-L-fucose from the
CC activated donor dTDP-2-deoxy-beta-L-fucose to the mono-glycosylated
CC aclacinomycin T (rhodosaminyl aklavinone), forming the di-glycosylated
CC aclacinomycin S (L-2-deoxyfucosyl-L-rhodosaminyl aklavinone). It can
CC also catalyze the addition of an alternate dTDP-L-sugar, dTDP-L-
CC daunosamine, to aclacinomycin T and the addition of 2-deoxy-beta-L-
CC fucose to the mono-glycosylated aglycones (monoglycosylated
CC anthracyclines) such as daunomycin (daunorubicin), adriamycin
CC (doxorubicin) and idarubicin. In vitro, AknK also catalyzes the
CC addition of a second L-2-deoxyfucosyl moiety from dTDP-2-deoxy-beta-L-
CC fucose, albeit with reduced activity, to the natural disaccharide chain
CC of aclacinomycin S to produce L-deoxyfucosyl-L-deoxyfucosyl-L-
CC rhodosaminyl aklavinone (2-deoxy-alpha-D-fucosyl-aclacinomycin S), a
CC variant of the natural aclacinomycin A. {ECO:0000269|PubMed:15078101}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=aclacinomycin T + dTDP-2-deoxy-beta-L-fucose = aclacinomycin S
CC + dTDP + H(+); Xref=Rhea:RHEA:41568, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58369, ChEBI:CHEBI:77979, ChEBI:CHEBI:78302,
CC ChEBI:CHEBI:78303; EC=2.4.1.327;
CC Evidence={ECO:0000269|PubMed:15078101};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=104.4 uM for rhodosaminyl aklavinone (with TDP-L-daunosamine as
CC sugar donor) {ECO:0000269|PubMed:15078101};
CC KM=109.1 uM for rhodosaminyl aklavinone (with TDP-L-2-deoxyfucose as
CC sugar donor) {ECO:0000269|PubMed:15078101};
CC KM=138 uM for idarubicin (with TDP-L-2-deoxyfucose as sugar donor)
CC {ECO:0000269|PubMed:15078101};
CC KM=148.9 uM for TDP-L-2-deoxyfucose (with rhodosaminyl aklavinone as
CC sugar acceptor) {ECO:0000269|PubMed:15078101};
CC KM=531 uM for TDP-L-2-deoxyfucose (with idarubicin as sugar acceptor)
CC {ECO:0000269|PubMed:15078101};
CC KM=940 uM for TDP-L-daunosamine (with rhodosaminyl aklavinone as
CC sugar acceptor) {ECO:0000269|PubMed:15078101};
CC Note=kcat is 2.1 sec(-1) for transferase activity with rhodosaminyl
CC aklavinone as sugar acceptor and TDP-L-daunosamine as sugar donor.
CC kcat is 5.4 sec(-1) for transferase activity with idarubicin as sugar
CC acceptor and TDP-L-2-deoxyfucose as sugar donor. kcat is 65.4 sec(-1)
CC for transferase activity with rhodosaminyl aklavinone as sugar
CC acceptor and TDP-L-2-deoxyfucose as sugar donor.
CC {ECO:0000269|PubMed:15078101};
CC -!- MASS SPECTROMETRY: Mass=50699; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:15078101};
CC -!- SIMILARITY: Belongs to the glycosyltransferase 28 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF257324; AAF70102.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9L555; -.
DR SMR; Q9L555; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR PRIDE; Q9L555; -.
DR KEGG; ag:AAF70102; -.
DR BioCyc; MetaCyc:MON-18193; -.
DR BRENDA; 2.4.1.B46; 13206.
DR SABIO-RK; Q9L555; -.
DR GO; GO:0016758; F:hexosyltransferase activity; IEA:UniProt.
DR GO; GO:0008194; F:UDP-glycosyltransferase activity; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR010610; DUF1205.
DR InterPro; IPR030953; Glycosyl_450act.
DR InterPro; IPR002213; UDP_glucos_trans.
DR Pfam; PF06722; DUF1205; 1.
DR TIGRFAMs; TIGR04516; glycosyl_450act; 1.
PE 1: Evidence at protein level;
KW Antibiotic biosynthesis; Direct protein sequencing; Glycosyltransferase;
KW Transferase.
FT CHAIN 1..440
FT /note="Aclacinomycin-T 2-deoxy-L-fucose transferase"
FT /id="PRO_0000430675"
SQ SEQUENCE 440 AA; 49164 MW; A167FE0E0FC42CF0 CRC64;
MKVLFTTFAA KSHMHAQVPL AWALQTAGHE VRIASQPDLA EDITRTGLTA VCVGEPLLLE
EQMQRVNEGL GDDAEIMESQ AEAGMDMTET RPEMLTWDHV LGVFTSMTAM AFQNSCPERM
IDDVVAFARE WQPDLIVWDT LSFAGPVAAQ VTGAAHARLL FGLDLLGRMR ETFLDLQEER
LPEQRDDPLR EWLTWTLGRY GAEFEEEVAV GQWTVDPVPP SMRFPVKQPF VPLRYIPYNG
QAVIPDWLHE PPKKRRVCLT LGVAHREVLD GDRASIGELV EALAELDVEV VATLNEKQLA
GMELPDNVRA VDFVPLNALL PTCSAVIHHG GSGTFQTALA HGVPQLIVPD MVWDTIHKAK
QLERFGAGLY LHDVDNYTAQ DLRDHLLRLL EEPSFAENCA RIRREMVGTP SPNDIVPLLE
KLTAEHRRDR GARGTVRGEQ
