SIHH_METKA
ID SIHH_METKA Reviewed; 424 AA.
AC P58855;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=S-inosyl-L-homocysteine hydrolase {ECO:0000255|HAMAP-Rule:MF_00563};
DE Short=SIHH {ECO:0000255|HAMAP-Rule:MF_00563};
DE EC=3.13.1.9 {ECO:0000255|HAMAP-Rule:MF_00563};
GN OrderedLocusNames=MK0368;
OS Methanopyrus kandleri (strain AV19 / DSM 6324 / JCM 9639 / NBRC 100938).
OC Archaea; Euryarchaeota; Methanopyri; Methanopyrales; Methanopyraceae;
OC Methanopyrus.
OX NCBI_TaxID=190192;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AV19 / DSM 6324 / JCM 9639 / NBRC 100938;
RX PubMed=11930014; DOI=10.1073/pnas.032671499;
RA Slesarev A.I., Mezhevaya K.V., Makarova K.S., Polushin N.N.,
RA Shcherbinina O.V., Shakhova V.V., Belova G.I., Aravind L., Natale D.A.,
RA Rogozin I.B., Tatusov R.L., Wolf Y.I., Stetter K.O., Malykh A.G.,
RA Koonin E.V., Kozyavkin S.A.;
RT "The complete genome of hyperthermophile Methanopyrus kandleri AV19 and
RT monophyly of archaeal methanogens.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4644-4649(2002).
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:0000255|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:0000255|HAMAP-Rule:MF_00563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59829;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00563};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00563};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000255|HAMAP-Rule:MF_00563};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00563}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|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:0000255|HAMAP-Rule:MF_00563}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000255|HAMAP-Rule:MF_00563}.
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DR EMBL; AE009439; AAM01583.1; -; Genomic_DNA.
DR AlphaFoldDB; P58855; -.
DR SMR; P58855; -.
DR STRING; 190192.MK0368; -.
DR PRIDE; P58855; -.
DR EnsemblBacteria; AAM01583; AAM01583; MK0368.
DR KEGG; mka:MK0368; -.
DR PATRIC; fig|190192.8.peg.391; -.
DR HOGENOM; CLU_025194_2_1_2; -.
DR OMA; NKYGCRE; -.
DR UniPathway; UPA00315; -.
DR Proteomes; UP000001826; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; IEA:InterPro.
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; -; 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 PANTHER; PTHR23420; PTHR23420; 1.
DR Pfam; PF05221; AdoHcyase; 1.
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; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 3: Inferred from homology;
KW Cytoplasm; Hydrolase; NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..424
FT /note="S-inosyl-L-homocysteine hydrolase"
FT /id="PRO_0000117005"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 156..158
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 185
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 190
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 219..224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 298..300
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 346
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
SQ SEQUENCE 424 AA; 47016 MW; 3DE7B10A3B44E1D5 CRC64;
MVVVKEGEYA IRDPSLAPKG RDMIEWARDH MPVLGAIRER FEEERPLEGI TVGMTLHLEA
KTAVLVETLM AGGAEVAITG CNPLSTKDEV AAALVEEGVH VYAWRGETEE EYYQNIDRVL
SHEPDIIVDD GADCIARVHT EFPDLAERVI GATEETTTGV NRLHAMHREG VLKFPVIAVN
DAKTKYLMDN RYGTGQSALD GLMRATNILL AGKTVVVVGY GWCGRGIARR ARGLGANVIV
VEVDPIKAME AIFDGFRVMP MDRAAEEGDI FITATGNRDV IRGEHIEKMK DGVILANAGH
FDVEIDKEYL EEHCEEKIDR RGGLVTEYRM PDGKRVYLIA EGRLVNLAAG EGHPIEIMDI
SFALQALSVE VLAKEGKEME PGVYKVPKDV DKRVAELKLE SMGIELEELT PEQREYMKSW
EEGT
