ID D5EA53_METMS Unreviewed; 411 AA.
AC D5EA53;
DT 15-JUN-2010, integrated into UniProtKB/TrEMBL.
DT 15-JUN-2010, sequence version 1.
DT 27-MAR-2024, entry version 84.
DE RecName: Full=S-inosyl-L-homocysteine hydrolase {ECO:0000256|HAMAP-Rule:MF_00563};
DE Short=SIHH {ECO:0000256|HAMAP-Rule:MF_00563};
DE EC=3.13.1.9 {ECO:0000256|HAMAP-Rule:MF_00563};
GN OrderedLocusNames=Mmah_0527 {ECO:0000313|EMBL:ADE36054.1};
OS Methanohalophilus mahii (strain ATCC 35705 / DSM 5219 / SLP).
OC Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC Methanosarcinales; Methanosarcinaceae; Methanohalophilus.
OX NCBI_TaxID=547558 {ECO:0000313|EMBL:ADE36054.1, ECO:0000313|Proteomes:UP000001059};
RN [1] {ECO:0000313|EMBL:ADE36054.1, ECO:0000313|Proteomes:UP000001059}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35705 / DSM 5219 / SLP
RC {ECO:0000313|Proteomes:UP000001059};
RG US DOE Joint Genome Institute (JGI-PGF);
RA Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Dalin E., Tice H.,
RA Bruce D., Goodwin L., Pitluck S., Kyrpides N., Mavromatis K., Ivanova N.,
RA Lykidis A., Saunders E., Brettin T., Detter J.C., Han C., Land M.,
RA Hauser L., Markowitz V., Cheng J.-F., Hugenholtz P., Woyke T., Wu D.,
RA Spring S., Schneider S., Schroeder M., Klenk H.-P., Eisen J.A.;
RT "The complete genome of Methanohalophilus mahii DSM 5219.";
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the hydrolysis of S-inosyl-L-homocysteine (SIH) to
CC L-homocysteine (Hcy) and inosine. Likely functions in a S-adenosyl-L-
CC methionine (SAM) recycling pathway from S-adenosyl-L-homocysteine (SAH)
CC produced from SAM-dependent methylation reactions. Can also catalyze
CC the reverse reaction in vitro, i.e. the synthesis of SIH from Hcy and
CC inosine. {ECO:0000256|HAMAP-Rule:MF_00563}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-inosyl-L-homocysteine = inosine + L-homocysteine;
CC Xref=Rhea:RHEA:59828, ChEBI:CHEBI:15377, ChEBI:CHEBI:17596,
CC ChEBI:CHEBI:57985, ChEBI:CHEBI:58199; EC=3.13.1.9;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00563};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00563,
CC ECO:0000256|PIRSR:PIRSR001109-2};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000256|HAMAP-Rule:MF_00563,
CC ECO:0000256|PIRSR:PIRSR001109-2};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis.
CC {ECO:0000256|HAMAP-Rule:MF_00563}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00563}.
CC -!- MISCELLANEOUS: SAH is a product of SAM methyltransferases and is known
CC to be a feedback inhibitor of these enzymes. As a result of this
CC inhibition, organisms have evolved efficient enzymes to metabolize SAH
CC via different pathways. The pathway found in methanogens differs from
CC the canonical pathway, it uses the deamination of S-adenosyl-L-
CC homocysteine to form S-inosyl-L-homocysteine for the regeneration of
CC SAM from S-adenosyl-L-homocysteine. {ECO:0000256|HAMAP-Rule:MF_00563}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000256|ARBA:ARBA00007122, ECO:0000256|HAMAP-Rule:MF_00563,
CC ECO:0000256|RuleBase:RU004166}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_00563}.
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DR EMBL; CP001994; ADE36054.1; -; Genomic_DNA.
DR RefSeq; WP_013036997.1; NC_014002.1.
DR AlphaFoldDB; D5EA53; -.
DR STRING; 547558.Mmah_0527; -.
DR GeneID; 8982668; -.
DR KEGG; mmh:Mmah_0527; -.
DR HOGENOM; CLU_025194_2_1_2; -.
DR OrthoDB; 8479at2157; -.
DR UniPathway; UPA00315; -.
DR Proteomes; UP000001059; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016802; F:trialkylsulfonium hydrolase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00401; SAHH; 1.
DR Gene3D; 3.40.50.1480; Adenosylhomocysteinase-like; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR HAMAP; MF_00563; AdoHcyase; 1.
DR InterPro; IPR042172; Adenosylhomocyst_ase-like_sf.
DR InterPro; IPR000043; Adenosylhomocysteinase-like.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020082; S-Ado-L-homoCys_hydrolase_CS.
DR NCBIfam; TIGR00936; ahcY; 1.
DR PANTHER; PTHR23420; ADENOSYLHOMOCYSTEINASE; 1.
DR PANTHER; PTHR23420:SF0; ADENOSYLHOMOCYSTEINASE; 1.
DR Pfam; PF05221; AdoHcyase; 2.
DR Pfam; PF00670; AdoHcyase_NAD; 1.
DR PIRSF; PIRSF001109; Ad_hcy_hydrolase; 1.
DR SMART; SM00996; AdoHcyase; 1.
DR SMART; SM00997; AdoHcyase_NAD; 1.
DR SUPFAM; SSF52283; Formate/glycerate dehydrogenase catalytic domain-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 3: Inferred from homology;
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00563};
KW Hydrolase {ECO:0000256|HAMAP-Rule:MF_00563, ECO:0000313|EMBL:ADE36054.1};
KW NAD {ECO:0000256|ARBA:ARBA00023027, ECO:0000256|HAMAP-Rule:MF_00563};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563, ECO:0000256|HAMAP-
KW Rule:MF_00563}; Reference proteome {ECO:0000313|Proteomes:UP000001059}.
FT DOMAIN 181..341
FT /note="S-adenosyl-L-homocysteine hydrolase NAD binding"
FT /evidence="ECO:0000259|SMART:SM00997"
FT BINDING 121
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 146
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 147..149
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563,
FT ECO:0000256|PIRSR:PIRSR001109-2"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 181
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 210..215
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 212..217
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|PIRSR:PIRSR001109-2"
FT BINDING 233
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563,
FT ECO:0000256|PIRSR:PIRSR001109-2"
FT BINDING 268
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563"
FT BINDING 289..291
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563,
FT ECO:0000256|PIRSR:PIRSR001109-2"
FT BINDING 335
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00563,
FT ECO:0000256|PIRSR:PIRSR001109-2"
FT BINDING 342
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|PIRSR:PIRSR001109-2"
SQ SEQUENCE 411 AA; 44965 MW; 22246135197663DC CRC64;
MIDEDLIESG EQKIEWARNH MPVLSIIRKE FEEEKPLKGH RIAMALHVEA KTAVLVETLA
AGGAEVAITG CNPLSTQNDV AVALDMKDNI DCFAKYGCSS KEYYDSIDRV LDIDPDITID
DGADLIFKLH TERTELLDSI LGGCEETTTG IHRLRAMEDE GALKMPVIAV NDAMTKFLFD
NRYGTGQSSW DGIIRTTNLL VAGKTVIIGG YGWCGRGAAM RASGLGANVI VTEVDPIRAL
EAKMDGFRVM PMQKAALYGD IFVMTTGNTD VLTRDHFEVM KDGAILANSG HFNVEINLED
LVALSSSVRD VRKNIKEYKV GGKHIHVLAD GRLVNLAAGD GHPAEVMDMS FANQAQCARY
IAENKLEVGV HAVPQDLDVR VARLKLESLG VEIDSYSPKQ AEYMCGWKCG T
//
