MQMTN_HELPJ
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 03-AUG-2022, entry version 118.
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; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC 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 = adenine + dehypoxanthine
CC futalosine; Xref=Rhea:RHEA:33079, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16708, 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=H2O + S-adenosyl-L-homocysteine = adenine + S-(5-deoxy-D-
CC ribos-5-yl)-L-homocysteine; 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=H2O + S-methyl-5'-thioadenosine = 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 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; -.
DR AlphaFoldDB; Q9ZMY2; -.
DR SMR; Q9ZMY2; -.
DR STRING; 85963.jhp_0082; -.
DR EnsemblBacteria; AAD05666; AAD05666; jhp_0082.
DR KEGG; hpj:jhp_0082; -.
DR eggNOG; COG0775; Bacteria.
DR OMA; DQFVHSK; -.
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 Proteomes; UP000000804; Chromosome.
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:0019509; P:L-methionine salvage from methylthioadenosine; IEA:UniProtKB-UniPathway.
DR GO; GO:0009234; P:menaquinone biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009164; P:nucleoside catabolic process; IEA:InterPro.
DR Gene3D; 3.40.50.1580; -; 1.
DR InterPro; IPR010049; MTA_SAH_Nsdase.
DR InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR Pfam; PF01048; PNP_UDP_1; 1.
DR SUPFAM; SSF53167; SSF53167; 1.
DR TIGRFAMs; TIGR01704; MTA/SAH-Nsdase; 1.
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
