GLYA_PLAF7
ID GLYA_PLAF7 Reviewed; 442 AA.
AC Q8I566;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Serine hydroxymethyltransferase {ECO:0000303|PubMed:11071283};
DE EC=2.1.2.1 {ECO:0000269|PubMed:11071283, ECO:0000269|PubMed:19591883, ECO:0000269|PubMed:24914963};
DE AltName: Full=PfSHMTc {ECO:0000303|PubMed:21129192};
GN Name=SHMT {ECO:0000303|PubMed:11071283};
GN ORFNames=PF3D7_1235600 {ECO:0000312|EMBL:CZT99515.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
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 [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11071283; DOI=10.1016/s0166-6851(00)00282-6;
RA Alfadhli S., Rathod P.K.;
RT "Gene organization of a Plasmodium falciparum serine
RT hydroxymethyltransferase and its functional expression in Escherichia
RT coli.";
RL Mol. Biochem. Parasitol. 110:283-291(2000).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=19591883; DOI=10.1016/j.molbiopara.2009.06.011;
RA Pang C.K., Hunter J.H., Gujjar R., Podutoori R., Bowman J., Mudeppa D.G.,
RA Rathod P.K.;
RT "Catalytic and ligand-binding characteristics of Plasmodium falciparum
RT serine hydroxymethyltransferase.";
RL Mol. Biochem. Parasitol. 168:74-83(2009).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=21129192; DOI=10.1186/1475-2875-9-351;
RA Read M., Mueller I.B., Mitchell S.L., Sims P.F., Hyde J.E.;
RT "Dynamic subcellular localization of isoforms of the folate pathway enzyme
RT serine hydroxymethyltransferase (SHMT) through the erythrocytic cycle of
RT Plasmodium falciparum.";
RL Malar. J. 9:351-351(2010).
RN [5] {ECO:0007744|PDB:4O6Z}
RP X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) OF MUTANT PHE-292 IN COMPLEX WITH
RP PYRIDOXAL PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, DISULFIDE
RP BOND, PYRIDOXAL PHOSPHATE AT LYS-237, AND MUTAGENESIS OF CYS-125; HIS-129;
RP PHE-292 AND CYS-364.
RX PubMed=24914963; DOI=10.1107/s1399004714005598;
RA Chitnumsub P., Ittarat W., Jaruwat A., Noytanom K., Amornwatcharapong W.,
RA Pornthanakasem W., Chaiyen P., Yuthavong Y., Leartsakulpanich U.;
RT "The structure of Plasmodium falciparum serine hydroxymethyltransferase
RT reveals a novel redox switch that regulates its activities.";
RL Acta Crystallogr. D 70:1517-1527(2014).
CC -!- FUNCTION: Catalyzes the interconversion of serine to glycine
CC accompanied with the production of 5,10-methylenetetrahydrofolate, a
CC source of one-carbon units used by thymidylate synthase to convert dUMP
CC to dTMP for DNA synthesis (PubMed:11071283, PubMed:19591883,
CC PubMed:24914963). Binds to its own mRNA and to the mRNA of bifunctional
CC dihydrofolate reductase-thymidylate synthase (DHFR-TS) in vitro; the
CC physiological relevance of this interaction is not clear
CC (PubMed:19591883). {ECO:0000269|PubMed:11071283,
CC ECO:0000269|PubMed:19591883, ECO:0000269|PubMed:24914963}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
CC Evidence={ECO:0000269|PubMed:11071283, ECO:0000269|PubMed:19591883,
CC ECO:0000269|PubMed:24914963};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|PIRSR:PIRSR000412-50,
CC ECO:0000269|PubMed:19591883, ECO:0000269|PubMed:24914963};
CC -!- ACTIVITY REGULATION: Redox regulation; active in reducing conditions,
CC inactive in oxidizing conditions. The reduction of the cysteine pairs
CC allows the access binding of the tetrahydrofolate substrate to its
CC binding site. This mechanism appears to be unique to Plasmodium
CC species. {ECO:0000269|PubMed:24914963}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=123 uM for L-serine {ECO:0000269|PubMed:24914963};
CC KM=700 uM for L-serine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19591883};
CC KM=86 uM for tetrahydrofolate (THF) {ECO:0000269|PubMed:24914963};
CC KM=3400 uM for tetrahydrofolate (THF) (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19591883};
CC KM=13 uM for pyridoxal 5'-phosphate (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19591883};
CC Vmax=139 pmol/min/ug enzyme towards L-serine (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:19591883};
CC Vmax=188.5 pmol/min/ug enzyme towards tetrahydrofolate (THF) (at 37
CC degrees Celsius) {ECO:0000269|PubMed:19591883};
CC Vmax=113 pmol/min/ug enzyme towards pyridoxal 5'-phosphate (at 37
CC degrees Celsius) {ECO:0000269|PubMed:19591883};
CC Note=kcat is 3.71 sec(-1) with L-serine and tetrahydrofolate as
CC substrates (at 37 degrees Celsius) (PubMed:19591883). kcat is 9.4
CC min(-1) with L-serine and tetrahydrofolate as substrates (at 37
CC degrees Celsius) (PubMed:19591883). {ECO:0000269|PubMed:19591883};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000305|PubMed:11071283, ECO:0000305|PubMed:24914963}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19591883,
CC ECO:0000269|PubMed:24914963}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21129192}.
CC Mitochondrion matrix {ECO:0000269|PubMed:21129192}. Plastid, apicoplast
CC {ECO:0000269|PubMed:21129192}. Nucleus {ECO:0000269|PubMed:21129192}.
CC Note=Predominantly localizes to the cytoplasm in early trophozoites and
CC postmitotic schizonts. Transiently localizes to the mitochondrion and
CC the apicoplast in late trophozoites and in mitotic schizonts. Partially
CC localizes to the nucleus, especially in late trophozoites and in
CC mitotic schizonts. {ECO:0000269|PubMed:21129192}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite erythrocyte stages,
CC namely in trophozoites and schizonts. {ECO:0000269|PubMed:21129192}.
CC -!- SIMILARITY: Belongs to the SHMT family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; LN999947; CZT99515.1; -; Genomic_DNA.
DR RefSeq; XP_001350750.1; XM_001350714.1.
DR PDB; 4O6Z; X-ray; 2.98 A; A/B/C/D=1-442.
DR PDBsum; 4O6Z; -.
DR AlphaFoldDB; Q8I566; -.
DR SMR; Q8I566; -.
DR STRING; 5833.PFL1720w; -.
DR SwissPalm; Q8I566; -.
DR PRIDE; Q8I566; -.
DR EnsemblProtists; CZT99515; CZT99515; PF3D7_1235600.
DR GeneID; 811396; -.
DR KEGG; pfa:PF3D7_1235600; -.
DR VEuPathDB; PlasmoDB:PF3D7_1235600; -.
DR HOGENOM; CLU_022477_0_2_1; -.
DR InParanoid; Q8I566; -.
DR OMA; SHPAGLI; -.
DR PhylomeDB; Q8I566; -.
DR SABIO-RK; Q8I566; -.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000001450; Chromosome 12.
DR GO; GO:0020011; C:apicoplast; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:GeneDB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004372; F:glycine hydroxymethyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0070905; F:serine binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0070178; P:D-serine metabolic process; IDA:GeneDB.
DR GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IBA:GO_Central.
DR GO; GO:0006565; P:L-serine catabolic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IDA:UniProtKB.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; IBA:GO_Central.
DR CDD; cd00378; SHMT; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR HAMAP; MF_00051; SHMT; 1.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR001085; Ser_HO-MeTrfase.
DR InterPro; IPR039429; SHMT-like_dom.
DR PANTHER; PTHR11680; PTHR11680; 1.
DR Pfam; PF00464; SHMT; 1.
DR PIRSF; PIRSF000412; SHMT; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apicoplast; Cytoplasm; Disulfide bond; Methyltransferase;
KW Mitochondrion; Nucleus; One-carbon metabolism; Plastid;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..442
FT /note="Serine hydroxymethyltransferase"
FT /id="PRO_0000449377"
FT BINDING 54
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:24914963,
FT ECO:0007744|PDB:4O6Z"
FT BINDING 100..102
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:24914963,
FT ECO:0007744|PDB:4O6Z"
FT BINDING 236
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:24914963,
FT ECO:0007744|PDB:4O6Z"
FT BINDING 272
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:24914963,
FT ECO:0007744|PDB:4O6Z"
FT MOD_RES 237
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000255|PIRSR:PIRSR000412-50,
FT ECO:0000269|PubMed:24914963, ECO:0007744|PDB:4O6Z"
FT DISULFID 125..364
FT /note="Inhibitory under oxidizing conditions"
FT /evidence="ECO:0000269|PubMed:24914963,
FT ECO:0007744|PDB:4O6Z"
FT MUTAGEN 125
FT /note="C->P: Severe loss of catalytic activity
FT characterized by a severe loss in substrate affinity."
FT /evidence="ECO:0000269|PubMed:24914963"
FT MUTAGEN 129
FT /note="H->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:24914963"
FT MUTAGEN 292
FT /note="F->E: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:24914963"
FT MUTAGEN 364
FT /note="C->A,S: No effect on catalytic activity. Active in
FT both reducing and non-reducing conditions."
FT /evidence="ECO:0000269|PubMed:24914963"
FT HELIX 7..10
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 12..26
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 40..46
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 68..84
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 101..113
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 163..172
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 191..200
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 229..236
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 257..265
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 275..288
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 291..313
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 339..348
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:4O6Z"
FT STRAND 369..374
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 375..379
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 387..408
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 412..417
FT /evidence="ECO:0007829|PDB:4O6Z"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:4O6Z"
FT HELIX 423..438
FT /evidence="ECO:0007829|PDB:4O6Z"
SQ SEQUENCE 442 AA; 49780 MW; 87E1C14AAFF0B8E7 CRC64;
MFNNDPLQKY DKELFDLLEK EKNRQIETIN LIASENLTNT AVRECLGDRI SNKYSEGYPH
KRYYGGNDYV DKIEELCYKR ALEAFNVSEE EWGVNVQPLS GSAANVQALY ALVGVKGKIM
GMHLCSGGHL THGFFDEKKK VSITSDLFES KLYKCNSEGY VDMESVRNLA LSFQPKVIIC
GYTSYPRDID YKGFREICDE VNAYLFADIS HISSFVACNL LNNPFTYADV VTTTTHKILR
GPRSALIFFN KKRNPGIDQK INSSVFPSFQ GGPHNNKIAA VACQLKEVNT PFFKEYTKQV
LLNSKALAEC LLKRNLDLVT NGTDNHLIVV DLRKYNITGS KLQETCNAIN IALNKNTIPS
DVDCVSPSGI RIGTPALTTR GCKEKDMEFI ADMLLKAILL TDELQQKYGK KLVDFKKGLV
NNPKIDELKK EVVQWAKNLP FA
