DADD_METJA
ID DADD_METJA Reviewed; 420 AA.
AC Q58936;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=5'-deoxyadenosine deaminase {ECO:0000255|HAMAP-Rule:MF_01281, ECO:0000303|PubMed:24375099};
DE Short=5'-dA deaminase {ECO:0000255|HAMAP-Rule:MF_01281, ECO:0000303|PubMed:24375099};
DE EC=3.5.4.41 {ECO:0000255|HAMAP-Rule:MF_01281, ECO:0000269|PubMed:24375099};
DE AltName: Full=5'-methylthioadenosine deaminase {ECO:0000305|PubMed:24375099};
DE Short=MTA deaminase {ECO:0000305|PubMed:24375099};
DE EC=3.5.4.31 {ECO:0000269|PubMed:24375099};
DE AltName: Full=Adenosine deaminase {ECO:0000305|PubMed:24375099};
DE EC=3.5.4.4 {ECO:0000269|PubMed:24375099};
DE AltName: Full=S-adenosylhomocysteine deaminase {ECO:0000305|PubMed:24375099, ECO:0000305|PubMed:25917907};
DE Short=SAH deaminase {ECO:0000305|PubMed:24375099, ECO:0000305|PubMed:25917907};
DE EC=3.5.4.28 {ECO:0000269|PubMed:24375099, ECO:0000269|PubMed:25917907};
GN Name=dadD {ECO:0000255|HAMAP-Rule:MF_01281, ECO:0000303|PubMed:24375099};
GN OrderedLocusNames=MJ1541;
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, SUBUNIT, AND MUTAGENESIS OF TYR-136; GLU-150 AND CYS-294.
RX PubMed=24375099; DOI=10.1128/jb.01308-13;
RA Miller D., O'Brien K., Xu H., White R.H.;
RT "Identification of a 5'-deoxyadenosine deaminase in Methanocaldococcus
RT jannaschii and its possible role in recycling the radical S-
RT adenosylmethionine enzyme reaction product 5'-deoxyadenosine.";
RL J. Bacteriol. 196:1064-1072(2014).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, 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 deamination of three SAM-derived enzymatic
CC products, namely 5'-deoxyadenosine, S-adenosyl-L-homocysteine, and 5'-
CC methylthioadenosine, to produce the inosine analogs. Can also deaminate
CC adenosine. The preferred substrate for this enzyme is 5'-
CC deoxyadenosine, but all these substrates are efficiently deaminated
CC (PubMed:24375099). Likely functions in a S-adenosyl-L-methionine (SAM)
CC recycling pathway from S-adenosyl-L-homocysteine (SAH) produced from
CC SAM-dependent methylation reactions (PubMed:25917907). May also be
CC involved in the recycling of 5'-deoxyadenosine, whereupon the 5'-
CC deoxyribose moiety of 5'-deoxyinosine is further metabolized to
CC deoxyhexoses used for the biosynthesis of aromatic amino acids in
CC methanogens (PubMed:24375099). {ECO:0000269|PubMed:24375099,
CC ECO:0000305|PubMed:25917907}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5'-deoxyadenosine + H(+) + H2O = 5'-deoxyinosine + NH4(+);
CC Xref=Rhea:RHEA:42892, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17319, ChEBI:CHEBI:28938, ChEBI:CHEBI:82775; EC=3.5.4.41;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01281,
CC ECO:0000269|PubMed:24375099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42893;
CC Evidence={ECO:0000305|PubMed:24375099};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O + S-adenosyl-L-homocysteine = NH4(+) + S-inosyl-L-
CC homocysteine; Xref=Rhea:RHEA:20716, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:57985; EC=3.5.4.28;
CC Evidence={ECO:0000269|PubMed:24375099, ECO:0000269|PubMed:25917907};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20717;
CC Evidence={ECO:0000305|PubMed:24375099, ECO:0000305|PubMed:25917907};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O + S-methyl-5'-thioadenosine = NH4(+) + S-methyl-5'-
CC thioinosine; Xref=Rhea:RHEA:25025, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:48595; EC=3.5.4.31;
CC Evidence={ECO:0000269|PubMed:24375099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25026;
CC Evidence={ECO:0000305|PubMed:24375099};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + H(+) + H2O = inosine + NH4(+);
CC Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4;
CC Evidence={ECO:0000269|PubMed:24375099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24409;
CC Evidence={ECO:0000305|PubMed:24375099};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01281};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01281};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.014 mM for 5'-deoxyadenosine (at pH 9 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:24375099};
CC KM=0.11 mM for S-methyl-5'-thioadenosine (at pH 9 and 60 degrees
CC Celsius) {ECO:0000269|PubMed:24375099};
CC KM=1.1 mM for S-adenosyl-L-homocysteine (at pH 9 and 60 degrees
CC Celsius) {ECO:0000269|PubMed:24375099};
CC KM=0.15 mM for adenosine (at pH 9 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:24375099};
CC Note=kcat is 120000 sec(-1) for 5'-deoxyadenosine deamination. kcat
CC is 160 sec(-1) for S-methyl-5'-thioadenosine deamination. kcat is
CC 1300 sec(-1) for S-adenosyl-L-homocysteine deamination. kcat is 110
CC sec(-1) for adenosine deamination (at pH 9 and 60 degrees Celsius).
CC {ECO:0000269|PubMed:24375099};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:24375099};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis.
CC {ECO:0000305|PubMed:25917907}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:24375099}.
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 (PubMed:25917907). 5'-deoxyadenosine
CC is a radical SAM enzyme reaction product which strongly inhibits
CC radical SAM enzymes. A pathway for removing this product must be
CC present in methanogens where the MTA/SAH nucleosidase which normally
CC metabolizes this compound is absent (PubMed:24375099).
CC {ECO:0000305|PubMed:24375099, ECO:0000305|PubMed:25917907}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC MTA/SAH deaminase family. {ECO:0000255|HAMAP-Rule:MF_01281}.
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DR EMBL; L77117; AAB99560.1; -; Genomic_DNA.
DR PIR; D64492; D64492.
DR RefSeq; WP_010871065.1; NC_000909.1.
DR AlphaFoldDB; Q58936; -.
DR SMR; Q58936; -.
DR STRING; 243232.MJ_1541; -.
DR EnsemblBacteria; AAB99560; AAB99560; MJ_1541.
DR GeneID; 1452449; -.
DR KEGG; mja:MJ_1541; -.
DR eggNOG; arCOG00695; Archaea.
DR HOGENOM; CLU_012358_2_1_2; -.
DR InParanoid; Q58936; -.
DR OMA; ALIGKVC; -.
DR OrthoDB; 40873at2157; -.
DR PhylomeDB; Q58936; -.
DR BRENDA; 3.5.4.28; 3260.
DR BRENDA; 3.5.4.31; 3260.
DR BRENDA; 3.5.4.4; 3260.
DR BRENDA; 3.5.4.41; 3260.
DR UniPathway; UPA00315; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0090613; F:5'-deoxyadenosine deaminase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0090614; F:5'-methylthioadenosine deaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0004000; F:adenosine deaminase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050270; F:S-adenosylhomocysteine deaminase activity; IEA:UniProtKB-EC.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.30.40.10; -; 1.
DR HAMAP; MF_01281; MTA_SAH_deamin; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR023512; Deaminase_MtaD/DadD.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..420
FT /note="5'-deoxyadenosine deaminase"
FT /id="PRO_0000122311"
FT BINDING 55
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 84
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 206
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 292
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01281"
FT MUTAGEN 136
FT /note="Y->R: Lowers temperature stability by 10 degrees
FT Celsius and decreases activity by 364-fold with 5'-
FT deoxyadenosine as substrate. Lowers temperature stability
FT by 35 degrees Celsius and decreases activity by 100000-fold
FT with 5'-deoxyadenosine as substrate; when associated with
FT R-150."
FT /evidence="ECO:0000269|PubMed:24375099"
FT MUTAGEN 150
FT /note="E->R: Lowers temperature stability by 10 degrees
FT Celsius and decreases activity by 571-fold with 5'-
FT deoxyadenosine as substrate. Lowers temperature stability
FT by 35 degrees Celsius and decreases activity by 100000-fold
FT with 5'-deoxyadenosine as substrate; when associated with
FT R-136."
FT /evidence="ECO:0000269|PubMed:24375099"
FT MUTAGEN 294
FT /note="C->S: No effect on temperature stability."
FT /evidence="ECO:0000269|PubMed:24375099"
SQ SEQUENCE 420 AA; 47468 MW; 2458E0E14AF91731 CRC64;
MILIKNVFVN GKRQDILIEG NKIKKIGEVK KEEIENAEII DGKNKIAIPG LINTHTHIPM
TLFRGVADDL PLMEWLNNYI WPMEAKLNEE IVYWGTLLGC IEMIRSGTTT FNDMYFFLEG
IAKAVDESGM RAVLAYGMID LFDEERRERE LKNAEKYINY INSLNNSRIM PALGPHAPYT
CSKELLMEVN NLAKKYNVPI HIHLNETLDE IKMVKEKTGM EPFIYLNSFG FFDDVRAIAA
HCVHLTDEEI KIMKQKNINV SHNPISNLKL ASGVAPIPKL LAEGINVTLG TDGCGSNNNL
NLFEEIKVSA ILHKGVNLNP TVVKAEEAFN FATKNGAKAL NIKAGEIREG YLADIVLINL
DKPYLYPKEN IMSHLVYAFN GFVDDVIIDG NIVMRDGEIL TVDEEKVYEK AEEMYEILRS
