SAHH_PLAF7
ID SAHH_PLAF7 Reviewed; 479 AA.
AC P50250; Q7K6A6; Q8MUG1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Adenosylhomocysteinase;
DE Short=AdoHcyase;
DE EC=3.3.1.1;
DE AltName: Full=PfSAHH;
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase;
GN ORFNames=PFE1050w;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8206944; DOI=10.1016/s0021-9258(17)34016-4;
RA Creedon K.A., Rathod P.K., Wellems T.E.;
RT "Plasmodium falciparum S-adenosylhomocysteine hydrolase. cDNA
RT identification, predicted protein sequence, and expression in Escherichia
RT coli.";
RL J. Biol. Chem. 269:16364-16370(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Bujnicki J.M., Prigge S.T., Caridha D., Chiang P.K.;
RT "S-adenosyl-L-homocysteine hydrolase from Plasmodium falciparum: structure,
RT evolution, and interactions with inhibitors.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NAD AND ADENOSINE,
RP SUBUNIT, AND MUTAGENESIS OF CYS-59.
RX PubMed=15476817; DOI=10.1016/j.jmb.2004.08.104;
RA Tanaka N., Nakanishi M., Kusakabe Y., Shiraiwa K., Yabe S., Ito Y.,
RA Kitade Y., Nakamura K.T.;
RT "Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human
RT malaria parasite Plasmodium falciparum.";
RL J. Mol. Biol. 343:1007-1017(2004).
CC -!- FUNCTION: Adenosylhomocysteine is a competitive inhibitor of S-
CC adenosyl-L-methionine-dependent methyl transferase reactions; therefore
CC adenosylhomocysteinase may play a key role in the control of
CC methylations via regulation of the intracellular concentration of
CC adenosylhomocysteine.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-adenosyl-L-homocysteine = adenosine + L-homocysteine;
CC Xref=Rhea:RHEA:21708, ChEBI:CHEBI:15377, ChEBI:CHEBI:16335,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58199; EC=3.3.1.1;
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Note=Binds 1 NAD(+) per subunit.;
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15476817}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
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DR EMBL; U07365; AAA21391.1; -; mRNA.
DR EMBL; AF525293; AAM90981.1; -; Genomic_DNA.
DR EMBL; AL844504; CAD51574.1; -; Genomic_DNA.
DR PIR; A54040; A54040.
DR RefSeq; XP_001351767.1; XM_001351731.1.
DR PDB; 1V8B; X-ray; 2.40 A; A/B/C/D=1-479.
DR PDBsum; 1V8B; -.
DR AlphaFoldDB; P50250; -.
DR SMR; P50250; -.
DR BioGRID; 1208339; 9.
DR IntAct; P50250; 8.
DR STRING; 5833.PFE1050w; -.
DR BindingDB; P50250; -.
DR ChEMBL; CHEMBL6076; -.
DR DrugBank; DB11638; Artenimol.
DR SwissPalm; P50250; -.
DR PRIDE; P50250; -.
DR EnsemblProtists; CAD51574; CAD51574; PF3D7_0520900.
DR GeneID; 813025; -.
DR KEGG; pfa:PF3D7_0520900; -.
DR VEuPathDB; PlasmoDB:PF3D7_0520900; -.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; P50250; -.
DR OMA; NKYGCRE; -.
DR PhylomeDB; P50250; -.
DR BRENDA; 3.3.1.1; 4889.
DR UniPathway; UPA00314; UER00076.
DR EvolutionaryTrace; P50250; -.
DR PRO; PR:P50250; -.
DR Proteomes; UP000001450; Chromosome 5.
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-KW.
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; 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 1: Evidence at protein level;
KW 3D-structure; Hydrolase; NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..479
FT /note="Adenosylhomocysteinase"
FT /id="PRO_0000116917"
FT BINDING 56
FT /ligand="substrate"
FT BINDING 134
FT /ligand="substrate"
FT BINDING 200
FT /ligand="substrate"
FT BINDING 201..203
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 230
FT /ligand="substrate"
FT BINDING 234
FT /ligand="substrate"
FT BINDING 235
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 264..269
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 287
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 322
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 343..345
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT BINDING 391
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:15476817"
FT SITE 59
FT /note="Important for nucleoside inhibitor binding"
FT MUTAGEN 59
FT /note="C->T: Decreases sensitivity towards inhibitors."
FT /evidence="ECO:0000269|PubMed:15476817"
FT CONFLICT 243..244
FT /note="LP -> YT (in Ref. 1; AAA21391)"
FT /evidence="ECO:0000305"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 29..37
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 57..68
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 107..118
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 137..155
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 202..213
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 234..251
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 267..279
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 306..309
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 314..318
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 328..331
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 352..356
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 362..367
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 400..419
FT /evidence="ECO:0007829|PDB:1V8B"
FT TURN 420..422
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:1V8B"
FT STRAND 428..431
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 435..446
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:1V8B"
FT HELIX 458..464
FT /evidence="ECO:0007829|PDB:1V8B"
SQ SEQUENCE 479 AA; 53839 MW; CC420C381466EEEF CRC64;
MVENKSKVKD ISLAPFGKMQ MEISENEMPG LMRIREEYGK DQPLKNAKIT GCLHMTVECA
LLIETLQKLG AQIRWCSCNI YSTADYAAAA VSTLENVTVF AWKNETLEEY WWCVESALTW
GDGDDNGPDM IVDDGGDATL LVHKGVEYEK LYEEKNILPD PEKAKNEEER CFLTLLKNSI
LKNPKKWTNI AKKIIGVSEE TTTGVLRLKK MDKQNELLFT AINVNDAVTK QKYDNVYGCR
HSLPDGLMRA TDFLISGKIV VICGYGDVGK GCASSMKGLG ARVYITEIDP ICAIQAVMEG
FNVVTLDEIV DKGDFFITCT GNVDVIKLEH LLKMKNNAVV GNIGHFDDEI QVNELFNYKG
IHIENVKPQV DRITLPNGNK IIVLARGRLL NLGCATGHPA FVMSFSFCNQ TFAQLDLWQN
KDTNKYENKV YLLPKHLDEK VALYHLKKLN ASLTELDDNQ CQFLGVNKSG PFKSNEYRY
