GLYA_HYDTT
ID GLYA_HYDTT Reviewed; 427 AA.
AC D3DKC4;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Serine hydroxymethyltransferase {ECO:0000255|HAMAP-Rule:MF_00051};
DE Short=SHMT {ECO:0000255|HAMAP-Rule:MF_00051};
DE Short=Serine methylase {ECO:0000255|HAMAP-Rule:MF_00051};
DE EC=2.1.2.1 {ECO:0000255|HAMAP-Rule:MF_00051};
DE AltName: Full=L-threonine/L-allo-threonine aldolase;
DE EC=4.1.2.48;
GN Name=glyA {ECO:0000255|HAMAP-Rule:MF_00051};
GN OrderedLocusNames=HTH_1832, Hydth_1815;
OS Hydrogenobacter thermophilus (strain DSM 6534 / IAM 12695 / TK-6).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Hydrogenobacter.
OX NCBI_TaxID=608538;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 6534 / IAM 12695 / TK-6;
RX PubMed=20348262; DOI=10.1128/jb.00158-10;
RA Arai H., Kanbe H., Ishii M., Igarashi Y.;
RT "Complete genome sequence of the thermophilic, obligately
RT chemolithoautotrophic hydrogen-oxidizing bacterium Hydrogenobacter
RT thermophilus TK-6.";
RL J. Bacteriol. 192:2651-2652(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 6534 / IAM 12695 / TK-6;
RX PubMed=21677850; DOI=10.4056/sigs.1463589;
RG US DOE Joint Genome Institute (JGI-PGF);
RA Zeytun A., Sikorski J., Nolan M., Lapidus A., Lucas S., Han J., Tice H.,
RA Cheng J.F., Tapia R., Goodwin L., Pitluck S., Liolios K., Ivanova N.,
RA Mavromatis K., Mikhailova N., Ovchinnikova G., Pati A., Chen A.,
RA Palaniappan K., Ngatchou-Djao O.D., Land M., Hauser L., Jeffries C.D.,
RA Han C., Detter J.C., Ubler S., Rohde M., Tindall B.J., Goker M., Wirth R.,
RA Woyke T., Bristow J., Eisen J.A., Markowitz V., Hugenholtz P., Klenk H.P.,
RA Kyrpides N.C.;
RT "Complete genome sequence of Hydrogenobacter thermophilus type strain (TK-
RT 6).";
RL Stand. Genomic Sci. 4:131-143(2011).
RN [3]
RP FUNCTION, THF-DEPENDENT SERINE HYDROXYMETHYLTRANSFERASE ACTIVITY,
RP THF-INDEPENDENT ALDOLASE ACTIVITY, REACTION MECHANISM, SUBSTRATE
RP SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=DSM 6534 / IAM 12695 / TK-6;
RX PubMed=22141341; DOI=10.1111/j.1742-4658.2011.08443.x;
RA Chiba Y., Terada T., Kameya M., Shimizu K., Arai H., Ishii M., Igarashi Y.;
RT "Mechanism for folate-independent aldolase reaction catalyzed by serine
RT hydroxymethyltransferase.";
RL FEBS J. 279:504-514(2012).
CC -!- FUNCTION: Its primary function is to catalyze the reversible
CC interconversion of serine and glycine with tetrahydrofolate (THF)
CC serving as the one-carbon carrier. This reaction serves as the major
CC source of one-carbon groups required for the biosynthesis of purines,
CC thymidylate, methionine, and other important biomolecules. Also
CC exhibits THF-independent aldolase activity toward beta-hydroxyamino
CC acids, producing glycine and aldehydes, via a retro-aldol mechanism.
CC Thus, is able to catalyze the cleavage of L-threonine, L-allo-
CC threonine, L-threo-beta-phenylserine and L-erythro-beta-phenylserine.
CC This second activity is likely to be physiological in H.thermophilus,
CC which is an organism that lacks the ortholog gene for the 'real'
CC threonine aldolase characterized in mesophilic bacteria (LtaE), yeast
CC and plants. {ECO:0000269|PubMed:22141341}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=L-threonine = acetaldehyde + glycine; Xref=Rhea:RHEA:19625,
CC ChEBI:CHEBI:15343, ChEBI:CHEBI:57305, ChEBI:CHEBI:57926; EC=4.1.2.48;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-allo-threonine = acetaldehyde + glycine;
CC Xref=Rhea:RHEA:26209, ChEBI:CHEBI:15343, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:58585; EC=4.1.2.48;
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00051};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.28 mM for L-serine (at pH 7.5 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:22141341};
CC KM=0.78 mM for glycine (at pH 7.5 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:22141341};
CC KM=7.64 mM for L-threonine (at pH 7.5 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:22141341};
CC KM=0.92 mM for L-allo-threonine (at pH 7.5 and 70 degrees Celsius)
CC {ECO:0000269|PubMed:22141341};
CC KM=0.59 mM for L-allo-threonine (at pH 7.5 and 75 degrees Celsius)
CC {ECO:0000269|PubMed:22141341};
CC KM=4.98 mM for DL-threo-beta-phenylserine (at pH 7.5 and 75 degrees
CC Celsius) {ECO:0000269|PubMed:22141341};
CC KM=2.63 mM for DL-erythro-beta-phenylserine (at pH 7.5 and 75 degrees
CC Celsius) {ECO:0000269|PubMed:22141341};
CC Note=kcat is 18.7 sec(-1) for the L-serine hydroxymethyltransferase
CC reaction, 2.3 sec(-1) for the L-threonine cleavage, and 18.0 sec(-1)
CC for the L-allo-threonine cleavage, at 70 degrees Celsius. In the THF-
CC independent aldolase reaction, the rate constants for the erythro
CC form substrates and for the substrates with beta-phenyl groups are
CC larger than those for the threo form substrates and for the
CC substrates with beta-methyl groups, respectively.;
CC pH dependence:
CC Optimum pH is 7.4 for the THF-independent L-allothreonine aldolase
CC activity. More than 95% of full activity remains at pH 8.4, although
CC the activities are reduced to about 90% at pH 6.9 and about 75% at pH
CC 5.9. {ECO:0000269|PubMed:22141341};
CC Temperature dependence:
CC Highly thermostable. Retains almost complete THF-independent L-allo-
CC threonine aldolase activity after being incubated at 75 degrees
CC Celsius for 10 minutes, and retains about 77% residual activity after
CC being treated at 87 degrees Celsius for the same time.
CC {ECO:0000269|PubMed:22141341};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000255|HAMAP-Rule:MF_00051}.
CC -!- PATHWAY: Amino-acid biosynthesis; glycine biosynthesis; glycine from L-
CC serine: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00051}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00051,
CC ECO:0000305|PubMed:22141341}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00051}.
CC -!- SIMILARITY: Belongs to the SHMT family. {ECO:0000255|HAMAP-
CC Rule:MF_00051, ECO:0000305}.
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DR EMBL; AP011112; BAI70276.1; -; Genomic_DNA.
DR EMBL; CP002221; ADO46196.1; -; Genomic_DNA.
DR RefSeq; WP_012964456.1; NC_017161.1.
DR AlphaFoldDB; D3DKC4; -.
DR SMR; D3DKC4; -.
DR STRING; 608538.HTH_1832; -.
DR EnsemblBacteria; BAI70276; BAI70276; HTH_1832.
DR KEGG; hte:Hydth_1815; -.
DR KEGG; hth:HTH_1832; -.
DR PATRIC; fig|608538.5.peg.1848; -.
DR eggNOG; COG0112; Bacteria.
DR HOGENOM; CLU_022477_2_1_0; -.
DR OMA; SHPAGLI; -.
DR OrthoDB; 861782at2; -.
DR UniPathway; UPA00193; -.
DR UniPathway; UPA00288; UER01023.
DR Proteomes; UP000002574; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004372; F:glycine hydroxymethyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008732; F:L-allo-threonine aldolase activity; IEA:RHEA.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IEA:UniProtKB-UniRule.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
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; IPR019798; Ser_HO-MeTrfase_PLP_BS.
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.
DR PROSITE; PS00096; SHMT; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Cytoplasm; Lyase; One-carbon metabolism;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1..427
FT /note="Serine hydroxymethyltransferase"
FT /id="PRO_0000416794"
FT BINDING 117
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00051"
FT BINDING 121..123
FT /ligand="(6S)-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:57453"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00051"
FT SITE 225
FT /note="Plays an important role in substrate specificity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00051"
FT MOD_RES 226
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00051"
SQ SEQUENCE 427 AA; 47535 MW; 604BA72A756F308F CRC64;
MRHLFNTDAE IYEAIVKEYE RQFYHLELIA SENFTSLAVM EAQGSVMTNK YAEGLPHKRY
YGGCEFVDIA EDLAIERAKA LFDAEHANVQ PHSGTQANMA VYMAVLKPGD TIMGMDLSHG
GHLTHGAKVN FSGKIYNAVY YGVHPETHLI DYDQLYRLAK EHKPKLIVGG ASAYPRVIDW
AKLREIADSV GAYLMVDMAH YAGLIAGGVY PNPVPYAHFV TSTTHKTLRG PRSGFILCKK
EFAKDIDKSV FPGIQGGPLM HVIAAKAVAF KEAMSQEFKE YARQVVANAR VLAEEFIKEG
FKVVSGGTDS HIVLLDLRDT GLTGREVEEA LGKANITVNK NAVPFDPLPP VKTSGIRLGT
PAMTTRGMKE DQMRIIARLI SKVIKNIGDE KVIEYVRQEV IEMCEQFPLY PELREEINHL
AKIKATY
