AGAL_FLAPL
ID AGAL_FLAPL Reviewed; 1078 AA.
AC P0DTR5;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 1.
DT 25-MAY-2022, entry version 8.
DE RecName: Full=A type blood alpha-D-galactosamine galactosaminidase {ECO:0000303|PubMed:31182795};
DE EC=3.2.1.- {ECO:0000269|PubMed:31182795};
DE AltName: Full=FpGalactosaminidase {ECO:0000303|PubMed:31182795};
DE Short=FpGalNase {ECO:0000303|PubMed:31182795};
DE AltName: Full=GH36 {ECO:0000303|PubMed:31182795};
DE Flags: Precursor;
OS Flavonifractor plautii (Fusobacterium plautii).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Oscillospiraceae;
OC Flavonifractor.
OX NCBI_TaxID=292800;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVE
RP SITE, BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, BIOTECHNOLOGY, AND MUTAGENESIS
RP OF ASP-463.
RX PubMed=31182795; DOI=10.1038/s41564-019-0469-7;
RA Rahfeld P., Sim L., Moon H., Constantinescu I., Morgan-Lang C.,
RA Hallam S.J., Kizhakkedathu J.N., Withers S.G.;
RT "An enzymatic pathway in the human gut microbiome that converts A to
RT universal O type blood.";
RL Nat. Microbiol. 4:1475-1485(2019).
CC -!- FUNCTION: One of an enzyme pair that work together to convert the A
CC antigen to the H antigen of the O blood type, which together release
CC galactosamine. Catalyzes the second step in the conversion, acts on the
CC product of the first reaction (FpGalNAcDeAc, AC P0DTR4). Is specific
CC for galactosamine containing sugars, does not cleave GalNAc residues.
CC {ECO:0000269|PubMed:31182795}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-D-galactosaminyl-(1->3)-[alpha-L-fucosyl-(1->2)]-
CC beta-D-galactosyl derivative + H2O = an alpha-L-fucosyl-(1->2)-beta-
CC D-galactosyl derivative + D-galactosamine; Xref=Rhea:RHEA:61568,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:140327, ChEBI:CHEBI:144802,
CC ChEBI:CHEBI:144817; Evidence={ECO:0000269|PubMed:31182795};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=64.5 uM for GalN antigen type 1 penta-MU
CC {ECO:0000269|PubMed:31182795};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:31182795};
CC -!- DOMAIN: Has an N-terminal glycoside hydrolase 36 domain with a probable
CC carbohydrate-binding domain in the C-terminus. The C-terminus is not
CC required for activity on soluble substrates but increases efficiency of
CC cleavage in red blood cells. {ECO:0000269|PubMed:31182795}.
CC -!- BIOTECHNOLOGY: 5 ug/ml of this enzyme pair converts A blood type to O
CC blood type in an hour, and can be removed by centrifugation, showing
CC the pair can be used for production of universal type donor blood.
CC {ECO:0000269|PubMed:31182795}.
CC -!- MISCELLANEOUS: DNA was isolated from a male human fecal sample of AB+
CC blood type, the sequence was given to UniProtKB by the submitters.
CC {ECO:0000269|PubMed:31182795}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 36 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Dropping barriers - Issue
CC 220 of December 2019;
CC URL="https://web.expasy.org/spotlight/back_issues/220/";
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DR RefSeq; WP_044942952.1; NZ_JADPCY010000139.1.
DR AlphaFoldDB; P0DTR5; -.
DR SMR; P0DTR5; -.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Glycosidase; Hydrolase; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1078
FT /note="A type blood alpha-D-galactosamine
FT galactosaminidase"
FT /id="PRO_0000448572"
FT REGION 306..570
FT /note="Glycoside hydrolase 36 domain"
FT /evidence="ECO:0000305|PubMed:31182795"
FT REGION 699..1078
FT /note="Not required for activity on soluble substrates"
FT /evidence="ECO:0000269|PubMed:31182795"
FT ACT_SITE 463
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:31182795"
FT ACT_SITE 532
FT /evidence="ECO:0000305|PubMed:31182795"
FT MUTAGEN 463
FT /note="D->A,G,S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31182795"
SQ SEQUENCE 1078 AA; 118707 MW; 86348685D13811B8 CRC64;
MRGKKFISLT LSTMLCLQLL PTASFAAAPA TDTGNAGLIA EGDYAIAGNG VRVTYDADGQ
TITLYRTEGS GLIQMSKPSP LGGPVIGGQE VQDFSHISCD VEQSTSGVMG SGQRMTITSQ
SMSTGLIRTY VLETSDIEEG VVYTATSYEA GASDVEVSWF IGSVYELYGA EDRIWSYNGG
GEGPMHYYDT LQKIDLTDSG KFSRENKQDD TAASIPVSDI YIADGGITVG DASATRREVH
TPVQETSDSA QVSIGWPGKV IAAGSVIEIG ESFAVVHPGD YYNGLRGYKN AMDHLGVIMP
APGDIPDSSY DLRWESWGWG FNWTIDLIIG KLDELQAAGV KQITLDDGWY TNAGDWALNP
EKFPNGASDA LRLTDAIHEH GMTALLWWRP CDGGIDSILY QQHPEYFVMD ADGRPARLPT
PGGGTNPSLG YALCPMADGA IASQVDFVNR AMNDWGFDGF KGDYVWSMPE CYNPAHNHAS
PEESTEKQSE IYRVSYEAMV ANDPNVFNLL CNCGTPQDYY SLPYMTQIAT ADPTSVDQTR
RRVKAYKALM GDYFPVTADH NNIWYPSAVG TGSVLIEKRD LSGTAKEEYE KWLGIADTVQ
LQKGRFIGDL YSYGFDPYET YVVEKDGVMY YAFYKDGSKY SPTGYPDIEL KGLDPNKMYR
IVDYVNDRVV ATNLMGDNAV FNTRFSDYLL VKAVEISEPD PEPVDPDYGF TSVDDRDEAL
IYTGTWHDDN NASFSEGTAR YTNSTDASVV FSFTGTSIRW YGQRDTNFGT AEVYLDDELK
TTVDANGAAE AGVCLFEALD LPAAEHTIKI VCKSGVIDID RFAYEAATLE PIYEKVDALS
DRITYVGNWE EYHNSEFYMG NAMRTDEAGA YAELTFRGTA VRLYAEMSFN FGTADVYLDG
ELVENIILYG QEATGQLMFE RTGLEEGEHT IRLVQNAWNI NLDYISYLPE QDQPTPPETT
VTVDAMDAQL VYTGVWNDDY HDVFQEGTAR YASSAGASVE FEFTGSEIRW YGQNDSNFGV
ASVYIDNEFV QQVNVNGAAA VGKLLFQKAD LPAGSHTIRI VCDTPVIDLD YLTYTTNA
