ID SIHH_METTH Reviewed; 417 AA.
AC O27673;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 143.
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=MTH_1636;
OS Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM
OS 10044 / NBRC 100330 / Delta H) (Methanobacterium thermoautotrophicum).
OC Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX NCBI_TaxID=187420;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX PubMed=9371463; DOI=10.1128/jb.179.22.7135-7155.1997;
RA Smith D.R., Doucette-Stamm L.A., Deloughery C., Lee H.-M., Dubois J.,
RA Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K., Harrison D.,
RA Hoang L., Keagle P., Lumm W., Pothier B., Qiu D., Spadafora R., Vicare R.,
RA Wang Y., Wierzbowski J., Gibson R., Jiwani N., Caruso A., Bush D.,
RA Safer H., Patwell D., Prabhakar S., McDougall S., Shimer G., Goyal A.,
RA Pietrovski S., Church G.M., Daniels C.J., Mao J.-I., Rice P., Noelling J.,
RA Reeve J.N.;
RT "Complete genome sequence of Methanobacterium thermoautotrophicum deltaH:
RT functional analysis and comparative genomics.";
RL J. Bacteriol. 179:7135-7155(1997).
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; AE000666; AAB86109.1; -; Genomic_DNA.
DR PIR; F69085; F69085.
DR RefSeq; WP_010877244.1; NC_000916.1.
DR AlphaFoldDB; O27673; -.
DR SMR; O27673; -.
DR STRING; 187420.MTH_1636; -.
DR PaxDb; 187420-MTH_1636; -.
DR EnsemblBacteria; AAB86109; AAB86109; MTH_1636.
DR GeneID; 77402157; -.
DR KEGG; mth:MTH_1636; -.
DR PATRIC; fig|187420.15.peg.1600; -.
DR HOGENOM; CLU_025194_2_1_2; -.
DR InParanoid; O27673; -.
DR UniPathway; UPA00315; -.
DR Proteomes; UP000005223; 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; 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..417
FT /note="S-inosyl-L-homocysteine hydrolase"
FT /id="PRO_0000117008"
FT BINDING 124
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 150..152
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 184
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 213..218
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 236
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 292..294
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 339
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
SQ SEQUENCE 417 AA; 46169 MW; 793A940867EFEB74 CRC64;
MPYKVKDISL APQGEKKIRW VQEHMPVLER IKSDFSEEKP FKGVTIGSCL HLEPKTINLG
LTLQAGGAEV AMTGCNPLST QDDATAAGAK MGLNMYGWRG ETNEEYYENI HRVLDHEPEI
LIDDGADMIF LVHRERPELL DGIIGACEET TTGINRLRAM AADGALKFPV MAVNDAYTKY
LFDNRYGTGQ STFDSIMGTT NMLIAGKTVV VCGYGWCGRG IAMRAEGLGA SVIVTEVDPI
RALEARMDGF RVMKVSDAVK EADILITATG NTDVVSESEF MNMKDGCVMA NSGHFNVEIN
REALEELSRE TGKVKEDIEV FIMPDGRKIY LLAEGRLVNL ASERGQGHPA EIMDMSFAMQ
ALSARHLLQE KPDPGVYRAP DEIDLMVARM KLDAMGIEID ELTEKQRLYL ENWEEGT
//
