SIHH_METJA
ID SIHH_METJA Reviewed; 415 AA.
AC Q58783;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=S-inosyl-L-homocysteine hydrolase {ECO:0000303|PubMed:25917907};
DE Short=SIHH {ECO:0000303|PubMed:25917907};
DE EC=3.13.1.9 {ECO:0000255|HAMAP-Rule:MF_00563, ECO:0000269|PubMed:25917907};
GN OrderedLocusNames=MJ1388;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, SUBUNIT, AND PATHWAY.
RX PubMed=25917907; DOI=10.1128/jb.00080-15;
RA Miller D., Xu H., White R.H.;
RT "S-Inosyl-L-Homocysteine Hydrolase, a Novel Enzyme Involved in S-Adenosyl-
RT L-Methionine Recycling.";
RL J. Bacteriol. 197:2284-2291(2015).
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. Is specific for SIH and inosine as it is unable to either
CC hydrolyze SAH or synthesize SAH from adenosine and Hcy.
CC {ECO:0000269|PubMed:25917907}.
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 ECO:0000269|PubMed:25917907};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59829;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00563,
CC ECO:0000305|PubMed:25917907};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:25917907};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000269|PubMed:25917907};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.64 mM for inosine (at pH 7.0 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:25917907};
CC KM=0.0054 mM for L-homocysteine (at pH 7.0 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:25917907};
CC KM=0.22 mM for S-inosyl-L-homocysteine (at pH 7.0 and 70 degrees
CC Celsius) {ECO:0000269|PubMed:25917907};
CC Note=kcat is 0.83 sec(-1) for the synthesis of SIH from inosine and
CC L-homocysteine. kcat is 0.42 sec(-1) for the hydrolysis of SIH (at pH
CC 7.0 and 70 degrees Celsius). {ECO:0000269|PubMed:25917907};
CC pH dependence:
CC Optimum pH is 7.0-7.5 and pH 9.6 for the reaction in the direction of
CC SIH synthesis. Shows no activity at either pH 6.5 or pH 11.5 in the
CC synthetic direction. The activity of SIHH in the hydrolysis direction
CC shows essentially the same activity over the pH range 6.5-11.5.
CC {ECO:0000269|PubMed:25917907};
CC Temperature dependence:
CC Optimum temperature is about 70 degrees Celsius.
CC {ECO:0000269|PubMed:25917907};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis.
CC {ECO:0000305|PubMed:25917907}.
CC -!- SUBUNIT: Exists both as a homotetramer and a homodimer, in a 4:1 ratio.
CC {ECO:0000269|PubMed:25917907}.
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:0000305|PubMed:25917907}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000255|HAMAP-Rule:MF_00563}.
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DR EMBL; L77117; AAB99397.1; -; Genomic_DNA.
DR PIR; C64473; C64473.
DR RefSeq; WP_010870905.1; NC_000909.1.
DR AlphaFoldDB; Q58783; -.
DR SMR; Q58783; -.
DR STRING; 243232.MJ_1388; -.
DR EnsemblBacteria; AAB99397; AAB99397; MJ_1388.
DR GeneID; 1452291; -.
DR KEGG; mja:MJ_1388; -.
DR eggNOG; arCOG04137; Archaea.
DR HOGENOM; CLU_025194_2_1_2; -.
DR InParanoid; Q58783; -.
DR OMA; NKYGCRE; -.
DR OrthoDB; 17629at2157; -.
DR PhylomeDB; Q58783; -.
DR BRENDA; 3.13.1.9; 3260.
DR BRENDA; 3.3.1.B1; 3260.
DR UniPathway; UPA00315; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; IBA:GO_Central.
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 GO; GO:0033353; P:S-adenosylmethionine cycle; IBA:GO_Central.
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; 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; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..415
FT /note="S-inosyl-L-homocysteine hydrolase"
FT /id="PRO_0000117004"
FT BINDING 123
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 149..151
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 178
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 183
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 212..217
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 235
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 291..293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT BINDING 337
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
SQ SEQUENCE 415 AA; 46607 MW; 16B1456E74D180F5 CRC64;
MYEVRDINLW KEGERKIQWA KQHMPVLNLI RERFKEEKPF KGITIGMALH LEAKTAVLAE
TLMEGGAEIA ITGCNPLSTQ DDVAAACAKK GMHVYAWRGE TVEEYYENLN KVLDHKPDIV
IDDGCDLIFL LHTKRTELLD NIMGGCEETT TGIIRLKAME KEGALKFPVM DVNDAYTKHL
FDNRYGTGQS ALDGILRATN LLIAGKTVVV AGYGWCGRGV AMRAKGLGAE VVVTEVNPIR
ALEARMDGFR VMKMEKAAEI GDIFITTTGC KDVIRKEHIL KMRNGAILAN AGHFDNEINK
KHLEELAKSI KEVRNCVTEY DLGNKKIYLL GEGRLVNLAC ADGHPCEVMD MSFANQALAA
EYILKNHEKL EPRVYNIPYE QDLMIASLKL KAMGIEIDEL TKEQKKYLED WREGT
