ID   MQMTN_HELPJ             Reviewed;         230 AA.
AC   Q9ZMY2;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   02-SEP-2026, entry version 132.
DE   RecName: Full=Aminodeoxyfutalosine nucleosidase;
DE            Short=AFL nucleosidase;
DE            Short=Aminofutalosine nucleosidase;
DE            EC=3.2.2.30 {ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
DE   AltName: Full=5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase;
DE            Short=MTA/SAH nucleosidase;
DE            Short=MTAN;
DE            EC=3.2.2.9 {ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
DE   AltName: Full=6-amino-6-deoxyfutalosine N-ribosylhydrolase;
GN   Name=mtnN; Synonyms=mtn; OrderedLocusNames=jhp_0082;
OS   Helicobacter pylori (strain J99 / ATCC 700824) (Campylobacter pylori J99).
OC   Bacteria; Pseudomonadati; Campylobacterota; Epsilonproteobacteria;
OC   Campylobacterales; Helicobacteraceae; Helicobacter.
OX   NCBI_TaxID=85963;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=J99 / ATCC 700824;
RX   PubMed=9923682; DOI=10.1038/16495;
RA   Alm R.A., Ling L.-S.L., Moir D.T., King B.L., Brown E.D., Doig P.C.,
RA   Smith D.R., Noonan B., Guild B.C., deJonge B.L., Carmel G., Tummino P.J.,
RA   Caruso A., Uria-Nickelsen M., Mills D.M., Ives C., Gibson R., Merberg D.,
RA   Mills S.D., Jiang Q., Taylor D.E., Vovis G.F., Trust T.J.;
RT   "Genomic sequence comparison of two unrelated isolates of the human gastric
RT   pathogen Helicobacter pylori.";
RL   Nature 397:176-180(1999).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF APOENZYME AND COMPLEXES WITH
RP   ADENINE AND THE NONHYDROLYZABLE TRANSITION STATE ANALOG FORMYCIN A,
RP   FUNCTION AS MTA NUCLEOSIDASE, CATALYTIC ACTIVITY, KINETIC PARAMETERS,
RP   REACTION MECHANISM, ACTIVE SITES, AND SUBUNIT.
RC   STRAIN=J99 / ATCC 700824;
RX   PubMed=20954236; DOI=10.1002/pro.524;
RA   Ronning D.R., Iacopelli N.M., Mishra V.;
RT   "Enzyme-ligand interactions that drive active site rearrangements in the
RT   Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine
RT   nucleosidase.";
RL   Protein Sci. 19:2498-2510(2010).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH A TRANSITION STATE
RP   ANALOG INHIBITOR, FUNCTION AS MTA AND AFL NUCLEOSIDASE, CATALYTIC ACTIVITY,
RP   KINETIC PARAMETERS, ACTIVITY REGULATION, AND MENAQUINONE BIOSYNTHESIS
RP   PATHWAY.
RC   STRAIN=J99 / ATCC 700824;
RX   PubMed=22891633; DOI=10.1021/bi3009664;
RA   Wang S., Haapalainen A.M., Yan F., Du Q., Tyler P.C., Evans G.B.,
RA   Rinaldo-Matthis A., Brown R.L., Norris G.E., Almo S.C., Schramm V.L.;
RT   "A picomolar transition state analogue inhibitor of MTAN as a specific
RT   antibiotic for Helicobacter pylori.";
RL   Biochemistry 51:6892-6894(2012).
CC   -!- FUNCTION: Catalyzes the direct conversion of aminodeoxyfutalosine (AFL)
CC       into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of
CC       the N-glycosidic bond; this reaction seems to represent an essential
CC       step in the menaquinone biosynthesis pathway in Helicobacter species.
CC       Also catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) to
CC       adenine and 5'-methylthioribose. Can also probably use S-
CC       adenosylhomocysteine (SAH) as substrate, leading to adenine and S-
CC       ribosylhomocysteine. These other activities highlight the tremendous
CC       versatility of the enzyme, which also plays key roles in S-
CC       adenosylmethionine recycling and in the biosynthesis of the quorum-
CC       sensing molecule autoinducer-2. {ECO:0000269|PubMed:20954236,
CC       ECO:0000269|PubMed:22891633}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=6-amino-6-deoxyfutalosine + H2O = dehypoxanthine futalosine +
CC         adenine; Xref=Rhea:RHEA:33079, ChEBI:CHEBI:15377, ChEBI:CHEBI:16708,
CC         ChEBI:CHEBI:58864, ChEBI:CHEBI:64286; EC=3.2.2.30;
CC         Evidence={ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-adenosyl-L-homocysteine + H2O = S-(5-deoxy-D-ribos-5-yl)-L-
CC         homocysteine + adenine; Xref=Rhea:RHEA:17805, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:16708, ChEBI:CHEBI:57856, ChEBI:CHEBI:58195; EC=3.2.2.9;
CC         Evidence={ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-methyl-5'-thioadenosine + H2O = 5-(methylsulfanyl)-D-ribose
CC         + adenine; Xref=Rhea:RHEA:13617, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:16708, ChEBI:CHEBI:17509, ChEBI:CHEBI:78440; EC=3.2.2.9;
CC         Evidence={ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5'-deoxyadenosine + H2O = 5-deoxy-D-ribose + adenine;
CC         Xref=Rhea:RHEA:29859, ChEBI:CHEBI:15377, ChEBI:CHEBI:16708,
CC         ChEBI:CHEBI:17319, ChEBI:CHEBI:149540; EC=3.2.2.9;
CC         Evidence={ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC   -!- ACTIVITY REGULATION: Is inhibited by the transition state analog BuT-
CC       DADMe-ImmA. This compound is also able to inhibit H.pylori growth and
CC       is more efficient than antibiotics commonly used in ulcer therapy.
CC       {ECO:0000269|PubMed:22891633}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.6 uM for 5'-methylthioadenosine {ECO:0000269|PubMed:20954236,
CC         ECO:0000269|PubMed:22891633};
CC         KM=0.8 uM for aminodeoxyfutalosine {ECO:0000269|PubMed:20954236,
CC         ECO:0000269|PubMed:22891633};
CC         KM=44.9 uM for 5'-methylthioadenosine (at pH 7.5 and 37 degrees
CC         Celsius) {ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC         Note=kcat is 12.1 sec(-1) with 5'-methylthioadenosine as substrate,
CC         and 4.3 sec(-1) with aminodeoxyfutalosine as substrate
CC         (PubMed:22891633). kcat is 4.92 sec(-1) with 5'-methylthioadenosine
CC         as substrate (at pH 7.5 and 37 degrees Celsius) (PubMed:20954236).
CC         {ECO:0000269|PubMed:20954236, ECO:0000269|PubMed:22891633};
CC   -!- PATHWAY: Quinol/quinone metabolism; menaquinone biosynthesis.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via salvage
CC       pathway; S-methyl-5-thio-alpha-D-ribose 1-phosphate from S-methyl-5'-
CC       thioadenosine (hydrolase route): step 1/2.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20954236,
CC       ECO:0000269|PubMed:22891633}.
CC   -!- SIMILARITY: Belongs to the PNP/UDP phosphorylase family. MtnN
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AE001439; AAD05666.1; -; Genomic_DNA.
DR   PIR; E71976; E71976.
DR   PDB; 3NM4; X-ray; 1.70 A; A/B=1-230.
DR   PDB; 3NM5; X-ray; 1.80 A; A/B=1-230.
DR   PDB; 3NM6; X-ray; 1.60 A; B=1-230.
DR   PDB; 4FFS; X-ray; 1.90 A; A=1-230.
DR   PDB; 4OJT; X-ray; 1.50 A; A=2-230.
DR   PDB; 4OY3; X-ray; 1.20 A; A=2-230.
DR   PDB; 4P54; X-ray; 1.65 A; A=2-230.
DR   PDB; 4WKN; X-ray; 2.00 A; A=2-230.
DR   PDB; 4WKO; X-ray; 1.90 A; A=2-230.
DR   PDB; 4WKP; X-ray; 1.58 A; A/B/C/D=2-230.
DR   PDB; 4YNB; X-ray; 2.00 A; A=2-230.
DR   PDB; 4YO8; X-ray; 2.10 A; A/B=2-230.
DR   PDB; 5CCD; Other; 2.20 A; A=2-230.
DR   PDB; 5CCE; Other; 2.50 A; A=2-230.
DR   PDB; 5JPC; Other; 2.50 A; A=2-230.
DR   PDB; 5K1Z; Other; 2.60 A; A=2-230.
DR   PDB; 5KB3; X-ray; 1.40 A; A=2-230.
DR   PDB; 6DYU; X-ray; 1.60 A; A/B=1-230.
DR   PDB; 6DYV; X-ray; 1.62 A; A/B=1-230.
DR   PDB; 6DYW; X-ray; 1.45 A; A/B=1-230.
DR   PDB; 6DYY; X-ray; 1.61 A; A/B/C/D=1-230.
DR   AlphaFoldDB; Q9ZMY2; -.
DR   MDposit; Q9ZMY2; -.
DR   SMR; Q9ZMY2; -.
DR   BindingDB; Q9ZMY2; -.
DR   ChEMBL; CHEMBL5291527; -.
DR   KEGG; hpj:jhp_0082; -.
DR   eggNOG; COG0775; Bacteria.
DR   BRENDA; 3.2.2.16; 2604.
DR   BRENDA; 3.2.2.30; 2604.
DR   BRENDA; 3.2.2.9; 2604.
DR   UniPathway; UPA00079; -.
DR   UniPathway; UPA00904; UER00871.
DR   EvolutionaryTrace; Q9ZMY2; -.
DR   PRO; PR:Q9ZMY2; -.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR   GO; GO:0102246; F:6-amino-6-deoxyfutalosine hydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008782; F:adenosylhomocysteine nucleosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008930; F:methylthioadenosine nucleosidase activity; IEA:InterPro.
DR   GO; GO:0009234; P:menaquinone biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0009164; P:nucleoside catabolic process; IEA:InterPro.
DR   CDD; cd09008; MTAN; 1.
DR   FunFam; 3.40.50.1580:FF:000026; Aminodeoxyfutalosine nucleosidase; 1.
DR   Gene3D; 3.40.50.1580; Nucleoside phosphorylase domain; 1.
DR   InterPro; IPR010049; MTA_SAH_Nsdase.
DR   InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR   InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR   NCBIfam; TIGR01704; MTA_SAH-Nsdase; 1.
DR   NCBIfam; NF004079; PRK05584.1; 1.
DR   PANTHER; PTHR46832; 5'-METHYLTHIOADENOSINE/S-ADENOSYLHOMOCYSTEINE NUCLEOSIDASE; 1.
DR   PANTHER; PTHR46832:SF1; 5'-METHYLTHIOADENOSINE_S-ADENOSYLHOMOCYSTEINE NUCLEOSIDASE; 1.
DR   Pfam; PF01048; PNP_UDP_1; 1.
DR   SUPFAM; SSF53167; Purine and uridine phosphorylases; 1.
DR   PDBsum; 3NM4; -.
DR   PDBsum; 3NM5; -.
DR   PDBsum; 3NM6; -.
DR   PDBsum; 4FFS; -.
DR   PDBsum; 4OJT; -.
DR   PDBsum; 4OY3; -.
DR   PDBsum; 4P54; -.
DR   PDBsum; 4WKN; -.
DR   PDBsum; 4WKO; -.
DR   PDBsum; 4WKP; -.
DR   PDBsum; 4YNB; -.
DR   PDBsum; 4YO8; -.
DR   PDBsum; 5CCD; -.
DR   PDBsum; 5CCE; -.
DR   PDBsum; 5JPC; -.
DR   PDBsum; 5K1Z; -.
DR   PDBsum; 5KB3; -.
DR   PDBsum; 6DYU; -.
DR   PDBsum; 6DYV; -.
DR   PDBsum; 6DYW; -.
DR   PDBsum; 6DYY; -.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis; Hydrolase; Menaquinone biosynthesis;
KW   Methionine biosynthesis.
FT   CHAIN           1..230
FT                   /note="Aminodeoxyfutalosine nucleosidase"
FT                   /id="PRO_0000164444"
FT   ACT_SITE        13
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000305|PubMed:20954236"
FT   ACT_SITE        198
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000305|PubMed:20954236"
FT   BINDING         80
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         154
FT                   /ligand="substrate"
FT   BINDING         174..175
FT                   /ligand="substrate"
FT   STRAND          4..10
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           11..21
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          26..30
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          33..40
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          43..49
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           54..68
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          71..81
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          91..99
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           105..107
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          119..122
FT                   /evidence="ECO:0007829|PDB:4WKP"
FT   HELIX           125..138
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          143..149
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           157..167
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          169..175
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           176..186
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   STRAND          190..198
FT                   /evidence="ECO:0007829|PDB:4OY3"
FT   HELIX           204..227
FT                   /evidence="ECO:0007829|PDB:4OY3"
SQ   SEQUENCE   230 AA;  25020 MW;  F1E128A8160512C9 CRC64;
     MQKIGILGAM REEITPILEL FGVDFEEIPL GGNVFHKGVY HNKEIIVAYS KIGKVHSTLT
     TTSMILAFGV QKVLFSGVAG SLVKDLKIND LLVATQLVQH DVDLSAFDHP LGFIPESAIF
     IETSGSLNAL AKKIANEQHI ALKEGVIASG DQFVHSKERK EFLVSEFKAS AVEMEGASVA
     FVCQKFGVPC CVLRSISDNA DEKAGMSFDE FLEKSAHTSA KFLKSMVDEL
//