View source for Serine hydroxymethyltransferase

{{Short description|InterPro Family}}
{{Infobox enzyme
| name = Serine hydroxymethyltransferase
| image = 6m5w2.jpg
| image_size = 270
| caption = Serine hydroxymethyltransferase 1 (cytosolic), homotetramer, Human
| EC_number = 2.1.2.1
| CAS_number = 9029-83-8
| GO_code = 
}}

[[File:EcSHMTPyMol.png|thumb|260px|PyMol rendered crystal structure of serine hydroxymethyltransferase]] 

'''Serine hydroxymethyltransferase''' (SHMT) is a [[pyridoxal phosphate]] (PLP) [[Vitamin B6|(Vitamin B<sub>6</sub>)]] dependent enzyme ({{EC number|2.1.2.1}}) which plays an important role in cellular one-carbon pathways by catalyzing the reversible, simultaneous conversions of <small>L</small>-[[serine]] to [[glycine]] and [[tetrahydrofolate]] (THF) to [[5,10-methylenetetrahydrofolate]] (5,10-CH<sub>2</sub>-THF).<ref name="Raoetal2003">{{cite journal | vauthors = Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS | title = Structure-function relationship in serine hydroxymethyltransferase | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1647 | issue = 1–2 | pages = 24–29 | date = April 2003 | pmid = 12686103 | doi = 10.1016/s1570-9639(03)00043-8 }}</ref>  This reaction provides the largest part of the one-carbon units available to the cell.<ref name="StoverSchirch1990">{{cite journal | vauthors = Stover P, Schirch V | title = Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate | journal = The Journal of Biological Chemistry | volume = 265 | issue = 24 | pages = 14227–14233 | date = August 1990 | doi = 10.1016/S0021-9258(18)77290-6 | pmid = 2201683 | doi-access = free }}</ref>

== Structure ==
The structure of the SHMT [[Protein subunit|monomer]] is similar across [[prokaryote]]s and [[eukaryote]]s, but whereas the active enzyme is a dimer in prokaryotes, the enzyme exists as a tetramer in eukaryotic cells, though the [[evolution]]ary basis for this difference in structure is unknown.<ref name="Raoetal2003"/> However, the evolutionary path taken by SHMT going from prokaryotic dimeric form to the eukaryotic tetrameric form can be easily seen as a sort of doubling event. In other words, the eukaryotic SHMT tetramer resembles two prokaryotic dimers that have packed together, forming what has been described as a “dimer of dimers.”<ref name="Renwick_1998">{{cite journal | vauthors = Renwick SB, Snell K, Baumann U | title = The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy | journal = Structure | volume = 6 | issue = 9 | pages = 1105–1116 | date = September 1998 | pmid = 9753690 | doi = 10.1016/s0969-2126(98)00112-9 | doi-access = free }}</ref> The interaction between two monomers within a dimer subunit has been found to occur over a greater contact area and is thus much tighter than the interaction between the two dimers.<ref name="Renwick_1998"/> Human serine hydroxymethyltransferase 2 (SHMT2) regulates one-carbon transfer reactions required for amino acid and nucleotide metabolism, and the regulated switch between dimeric and tetrameric forms of SHMT2, which is induced by [[pyridoxal phosphate]],<ref>{{cite journal | vauthors = Giardina G, Brunotti P, Fiascarelli A, Cicalini A, Costa MG, Buckle AM, di Salvo ML, Giorgi A, Marani M, Paone A, Rinaldo S, Paiardini A, Contestabile R, Cutruzzolà F | display-authors = 6 | title = How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state | journal = The FEBS Journal | volume = 282 | issue = 7 | pages = 1225–1241 | date = April 2015 | pmid = 25619277 | doi = 10.1111/febs.13211 | s2cid = 11561274 | doi-access = free }}</ref> has recently been shown to be involved in regulation of the BRISC deubiquitylase complex, linking metabolism to inflammation. The SHMT2 dimer, but not the PLP-bound tetramer, is a potent inhibitor of the multimeric BRISC complex, revealing a potential mechanism for SHMT2 regulation of inflammation.<ref>{{cite journal | vauthors = Eyers PA, Murphy JM | title = The evolving world of pseudoenzymes: proteins, prejudice and zombies | journal = BMC Biology | volume = 14 | issue = 1 | pages = 98 | date = November 2016 | pmid = 27835992 | pmc = 5106787 | doi = 10.1038/s41586-019-1232-1 | bibcode = 2019Natur.570..194W }}</ref>

A single SHMT monomer can be subdivided into three domains: an [[N-terminus]] “arm,” a “large” [[Protein domain|domain]], and a “small” domain.<ref name="Renwick_1998"/> The N-terminus arm appears to maintain the tight interaction between two monomers. The arm, consisting of two [[Alpha helix|alpha helices]] and a [[beta sheet]], wraps around the other monomer when in oligomeric form.<ref name="Renwick_1998"/> The “large” domain contains the PLP [[binding site]], as seen in other PLP-dependent proteins, like [[aspartate aminotransferase]].<ref name="Renwick_1998"/> The large domain in the eukaryotic form also contains a histidine that is essential for tetramer stability.<ref name="Renwick_1998"/> All four histidines of these residues, one from each monomer, sit at the center of the tetrameric complex, where two histidines from a dimeric subunit engages in [[Stacking (chemistry)|stacking]] interactions with the histidines of the other subunit.<ref name="Renwick_1998"/> Prokaryotic SHMT has a [[proline]] residue rather than histidine in the equivalent position, which would in part explain why prokaryotic SHMT does not form tetramers.<ref name="Scarsdale_2000">{{cite journal | vauthors = Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT | title = Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate | journal = Journal of Molecular Biology | volume = 296 | issue = 1 | pages = 155–168 | date = February 2000 | pmid = 10656824 | doi = 10.1006/jmbi.1999.3453 }}</ref>

The active site structure is highly conserved across eukaryotic and prokaryotic forms. The PLP is anchored by means of a [[lysine]], which forms an [[aldimine]] [[Schiff base]] linkage with the PLP [[aldehyde]].<ref name="Florio_2011">{{cite journal | vauthors = Florio R, di Salvo ML, Vivoli M, Contestabile R | title = Serine hydroxymethyltransferase: a model enzyme for mechanistic, structural, and evolutionary studies | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1814 | issue = 11 | pages = 1489–1496 | date = November 2011 | pmid = 21059411 | doi = 10.1016/j.bbapap.2010.10.010 }}</ref> It has been hypothesized that a nearby [[tyrosine]] functions as the [[proton]] donor and acceptor during the transadimination step as well as the [[Formaldehyde|formyl]] transfer step and that an [[arginine]] residue engages the tyrosine side chain in a [[Cation–pi interaction|cation–π interaction]], which helps to lower the [[Acid dissociation constant|pK{{sub|a}}]] of the tyrosine, lowering the barrier for proton transfer.<ref name="Florio_2011"/>

==Mechanism==
The mechanism commonly ascribed to SHMT enzymatic activity is a transamidation followed by a cleavage of [[amino acid]] side chain from the backbone.<ref name="Florio_2011"/> The N-terminal amine of serine makes a [[Nucleophile|nucleophilic]] attack on the aldimine between the SHMT lysine (Internal Aldimine) and the PLP aldehyde to form a gem-diamine, and then the N-terminal amine [[lone pair]] comes down to displace the lysine, forming a new aldimine, this time with the serine (External Aldimine).<ref name="Florio_2011"/><ref name="Schirch_2005">{{cite journal | vauthors = Schirch V, Szebenyi DM | title = Serine hydroxymethyltransferase revisited | journal = Current Opinion in Chemical Biology | volume = 9 | issue = 5 | pages = 482–487 | date = October 2005 | pmid = 16125438 | doi = 10.1016/j.cbpa.2005.08.017 }}</ref> It is believed that a nearby tyrosine is responsible for much of the proton transfers that occur during the transaldimination.<ref name="Florio_2011"/><ref>{{cite journal | vauthors = Oliveira EF, Cerqueira NM, Fernandes PA, Ramos MJ | title = Mechanism of formation of the internal aldimine in pyridoxal 5'-phosphate-dependent enzymes | language = EN | journal = Journal of the American Chemical Society | volume = 133 | issue = 39 | pages = 15496–15505 | date = October 2011 | pmid = 21854048 | doi = 10.1021/ja204229m }}</ref><ref>{{cite journal | vauthors = Cerqueira NM, Fernandes PA, Ramos MJ | title = Computational Mechanistic Studies Addressed to the Transimination Reaction Present in All Pyridoxal 5'-Phosphate-Requiring Enzymes | language = EN | journal = Journal of Chemical Theory and Computation | volume = 7 | issue = 5 | pages = 1356–1368 | date = May 2011 | pmid = 26610130 | doi = 10.1021/ct1002219 }}</ref>
[[File:Serine hydroxymethyltransferase formaldehyde intermediate mechanism.svg|frame|A glutamate in the SHMT active site deprotonates the serine hydroxyl from the external aldimine forming a formaldehyde intermediate. Tetrahydrofolate (THF) then attacks the formaldehyde forming a carbinolamine followed by several proton transfers and dehydration of the carbinolamine, all steps facilitated by the enzyme. The methylene-THF intermediate cyclizes to 5,10-CH<sub>2</sub>-THF. Lastly, the glycine external aldimine reforms before hydrolysis and release from the active site.<ref name="Schirch_2005" /><ref>{{cite journal | vauthors = Trivedi V, Gupta A, Jala VR, Saravanan P, Rao GS, Rao NA, Savithri HS, Subramanya HS | display-authors = 6 | title = Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism | language = English | journal = The Journal of Biological Chemistry | volume = 277 | issue = 19 | pages = 17161–17169 | date = May 2002 | pmid = 11877399 | doi = 10.1074/jbc.M111976200 | doi-access = free }}</ref><ref name="Fernandes 10096–10110" />]]

Once the serine is bonded to PLP, PLP triggers the α-elimination of the hydroxymethyl group of the substrate (serine). This group is released as a formaldehyde molecule because a nearby glutamate abstracts the proton from the hydroxyl group. Afterwards, the nucleophilic amine on THF attacks the free formaldehyde intermediate to make the [[Hemiaminal|carbinolamine]] intermediate.<ref name="Schirch_2005"/><ref name="Fernandes 10096–10110">{{Cite journal| vauthors = Fernandes HS, Ramos MJ, Cerqueira NM |date=2018-10-03|title=Catalytic Mechanism of the Serine Hydroxymethyltransferase: A Computational ONIOM QM/MM Study|journal=ACS Catalysis|volume=8|issue=11|language=en|pages=10096–10110|doi=10.1021/acscatal.8b02321|s2cid=105838672 |issn=2155-5435}}</ref> In the second case, the nucleophilic amines on THF attack the serine side chain carbon, simultaneously forming a carbinolamine intermediate on the THF and a quinoid intermediate with the PLP.<ref name="Schirch_2005"/><ref name="Szebenyi_2004">{{cite journal | vauthors = Szebenyi DM, Musayev FN, di Salvo ML, Safo MK, Schirch V | title = Serine hydroxymethyltransferase: role of glu75 and evidence that serine is cleaved by a retroaldol mechanism | journal = Biochemistry | volume = 43 | issue = 22 | pages = 6865–6876 | date = June 2004 | pmid = 15170323 | doi = 10.1021/bi049791y | title-link = Aldol reaction }}</ref> However, THF is not an obligate [[Substrate (chemistry)|substrate]] for SHMT, meaning the cleavage of serine and other β-hydroxy amino acids (such as [[threonine]]) can occur without the presence of THF and, in this case, the mechanism is a retro-aldol cleavage.<ref name="Chiba_2012">{{cite journal | vauthors = Chiba Y, Terada T, Kameya M, Shimizu K, Arai H, Ishii M, Igarashi Y | title = Mechanism for folate-independent aldolase reaction catalyzed by serine hydroxymethyltransferase | journal = The FEBS Journal | volume = 279 | issue = 3 | pages = 504–514 | date = February 2012 | pmid = 22141341 | doi = 10.1111/j.1742-4658.2011.08443.x | doi-access = free }}</ref> Also, it seems that the subsequent [[Dehydration reaction|dehydration]] of the carbinolamine intermediate to form the [[methylene bridge]] and fully cyclize into 5,10-CH<sub>2</sub>-THF is not catalyzed by the enzyme and this reaction may occur [[Spontaneous process|spontaneously]].<ref name="Schirch_2005"/> In fact, this conversion could occur outside the enzyme, but a study shows that this reaction is faster and thermodynamically favourable when occurs inside the SHMT aided by the Glu57 residue. Moreover, the cyclisation of the carbinolamine intermediate to form 5,10-CH<sub>2</sub>-THF is essential to Glu57 restore its proton that is used to protonate the quinonoid intermediate and complete the catalytic cycle.<ref name="Fernandes 10096–10110"/>

==Clinical significance==
[[Folic acid|Folate metabolism]] has already been the subject of [[Chemotherapy|chemotherapeutic]] strategies, but SHMT [[Enzyme inhibitor|inhibition]], while researched, had not really been taken advantage of in commercial anticancer drugs.<ref name="Daidone_2011">{{cite journal | vauthors = Daidone F, Florio R, Rinaldo S, Contestabile R, di Salvo ML, Cutruzzolà F, Bossa F, Paiardini A | display-authors = 6 | title = In silico and in vitro validation of serine hydroxymethyltransferase as a chemotherapeutic target of the antifolate drug pemetrexed | journal = European Journal of Medicinal Chemistry | volume = 46 | issue = 5 | pages = 1616–1621 | date = May 2011 | pmid = 21371789 | doi = 10.1016/j.ejmech.2011.02.009 }}</ref> However, because the folates used by folate metabolic and folate-dependent enzymes are all very similar in structure and folate mimics are already common in medical use, it has not been difficult to find potential molecular structures that may inhibit SHMT.<ref name="Daidone_2011"/> For example, [[pemetrexed]] is already used as an antifolate to treat mesothelioma and was found to be an effective inhibitor of SHMT<ref name="Daidone_2011"/> and screening other antifolates revealed lometrexol as another effective inhibitor of SHMT.<ref name="Paiardini_2015">{{cite journal | vauthors = Paiardini A, Fiascarelli A, Rinaldo S, Daidone F, Giardina G, Koes DR, Parroni A, Montini G, Marani M, Paone A, McDermott LA, Contestabile R, Cutruzzolà F | display-authors = 6 | title = Screening and in vitro testing of antifolate inhibitors of human cytosolic serine hydroxymethyltransferase | journal = ChemMedChem | volume = 10 | issue = 3 | pages = 490–497 | date = March 2015 | pmid = 25677305 | pmc = 5438088 | doi = 10.1002/cmdc.201500028 }}</ref>

SHMT has also undergone investigation as a potential target for [[Antimalarial medication|antimalarial drugs]]. Research indicates that the active site environment of ''[[Plasmodium]]'' SHMTs (PSHMTs) differs from that of human cytosolic SHMT, allowing for the possibility of selective inhibition of PSHMT and, thus, the treatment of [[malaria]] infections.<ref name="Pinthong_2014">{{cite journal | vauthors = Pinthong C, Maenpuen S, Amornwatcharapong W, Yuthavong Y, Leartsakulpanich U, Chaiyen P | title = Distinct biochemical properties of human serine hydroxymethyltransferase compared with the Plasmodium enzyme: implications for selective inhibition | journal = The FEBS Journal | volume = 281 | issue = 11 | pages = 2570–2583 | date = June 2014 | pmid = 24698160 | doi = 10.1111/febs.12803 | doi-access = free }}</ref> In particular, certain pyrazolopyran molecules have been shown to have a selective nanomolar efficacy against PSHMTs. Poor [[pharmacokinetics]], however, have prevented these pyrazolopyrans from being effective in living models.<ref name="Witschel_2015">{{cite journal | vauthors = Witschel MC, Rottmann M, Schwab A, Leartsakulpanich U, Chitnumsub P, Seet M, Tonazzi S, Schwertz G, Stelzer F, Mietzner T, McNamara C, Thater F, Freymond C, Jaruwat A, Pinthong C, Riangrungroj P, Oufir M, Hamburger M, Mäser P, Sanz-Alonso LM, Charman S, Wittlin S, Yuthavong Y, Chaiyen P, Diederich F | display-authors = 6 | title = Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities | journal = Journal of Medicinal Chemistry | volume = 58 | issue = 7 | pages = 3117–3130 | date = April 2015 | pmid = 25785478 | doi = 10.1021/jm501987h }}</ref>

== Isoforms ==
Bacteria such as ''[[Escherichia coli]]'' and ''[[Bacillus stearothermophilus]]'' have versions of this enzyme and there appear to be two isoforms of SHMT in mammals, one in the [[cytoplasm]] (cSHMT) and another in the [[mitochondria]] (mSHMT).<ref name="Raoetal2003"/>  Plants may have an additional SHMT isoform within [[chloroplast]]s.<ref name="Besson_1995">{{cite journal |vauthors=Besson V, Nauburger M, Rebeille F, Douce R | title = Evidence for three serine hydroxymethyltransferases in green leaf cells. Purification and characterization of the mitochondrial and chloroplastic isoforms | journal = Plant Physiol. Biochem. | year = 1995 | volume = 33 | issue = 6 | pages = 665–673 }}</ref>

In mammals, the enzyme is a [[tetramer]] of four identical subunits of approximately 50,000 daltons each.  The intact [[enzyme|holoenzyme]] has a molecular weight of approximately 200,000 daltons and incorporates four molecules of PLP as a [[Cofactor (biochemistry)|coenzyme]].<ref name="pmid5028104">{{cite journal | vauthors = Martinez-Carrion M, Critz W, Quashnock J | title = Molecular weight and subunits of serine transhydroxymethylase | journal = Biochemistry | volume = 11 | issue = 9 | pages = 1613–1615 | date = April 1972 | pmid = 5028104 | doi = 10.1021/bi00759a011 }}</ref>

== Other reactions ==
As well as its primary role in folate metabolism, SHMT also catalyzes other reactions that may be biologically significant, including the conversion of 5,10-Methenyltetrahydrofolate to [[10-Formyltetrahydrofolate]].<ref name="StoverSchirch1990"/> When coupled with C<sub>1</sub>-tetrahydrofolate synthase and tetrahydropteroate, cSHMT also catalyzes the conversion of formate to serine.<ref name="StoverSchirch1990"/>

== Role in Smith–Magenis syndrome ==
[[Smith–Magenis syndrome]] (SMS) is a rare disorder that manifests as a complex set of traits including facial abnormalities, unusual behaviors, and developmental delay.<ref name="Elseaetal1995">{{cite journal | vauthors = Elsea SH, Juyal RC, Jiralerspong S, Finucane BM, Pandolfo M, Greenberg F, Baldini A, Stover P, Patel PI | display-authors = 6 | title = Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith-Magenis syndrome | journal = American Journal of Human Genetics | volume = 57 | issue = 6 | pages = 1342–1350 | date = December 1995 | pmid = 8533763 | pmc = 1801426 }}</ref>  It results from an interstitial deletion within chromosome 17p11.2, including the cSHMT gene and a small study showed SHMT activity in SMS patients was ~50% of normal.<ref name="Elseaetal1995"/>  Reduced SHMT would result in a reduced glycine pool, which could affect the nervous system by reducing the functioning of [[NMDA receptor]]s. This could be a potential mechanism for explaining SMS.<ref name="Elseaetal1995"/>

== Figures ==
[[File:Biological role of serine hydroxymethyltransferase.png|750px|thumb|center|Biological role of SHMT:<br /> '''a''') Serine–glycine interconversion catalyzed by SHMT. THF = tetrahydrofolate, CH2-THF = N-5,N-10-methylenetetrahydrofolate. The red dot highlights the carbon that is transferred from Ser to THF. <br /> '''b''') Schematic overview of human SHMT (hSHMT) function. MTHFD = methylenetetrahydrofolate dehydrogenase-cyclohydrolase, CH2-THF = N-5,N-10-methylenetetrahydrofolate, CH+-THF = 5,10-methenyltetrahydrofolate, CHO-THF = 10-formyltetrahydrofolate, NADP+ = Nicotinamide adenine dinucleotide phosphate, NADPH = NADP+ reduced form. <br /> '''c''') SHMT, dihydrofolate reductase (DHFR), and thymidylate synthase (TS) in the folate cycle. THF = tetrahydrofolate, CH2-THF = 5,10-methylenetetrahydrofolate, DHF = dihydrofolate, FdUMP = fluorodeoxyuridine-5′-monophosphate, dUMP = deoxyuridine monophosphate, dTMP = deoxythymidine monophosphate.<br /> From Nonaka et al., 2019.<ref name="pmid30787298">{{cite journal | vauthors = Nonaka H, Nakanishi Y, Kuno S, Ota T, Mochidome K, Saito Y, Sugihara F, Takakusagi Y, Aoki I, Nagatoishi S, Tsumoto K, Sando S | display-authors = 6 | title = Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction | journal = Nature Communications | volume = 10 | issue = 1 | pages = 876 | date = February 2019 | pmid = 30787298 | pmc = 6382819 | doi = 10.1038/s41467-019-08833-7 }}</ref>]]

== References ==
{{Reflist|2}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Akhtar M, el-Obeid HA | title = Inactivation of serine transhydroxymethylase and threonine aldolase activities | journal = Biochimica et Biophysica Acta (BBA) - Enzymology | volume = 258 | issue = 3 | pages = 791–799 | date = March 1972 | pmid = 5017703 | doi = 10.1016/0005-2744(72)90180-5 }}
* {{cite journal | vauthors = Blakley RL | title = A spectrophotometric study of the reaction catalysed by serine transhydroxymethylase | journal = The Biochemical Journal | volume = 77 | issue = 3 | pages = 459–465 | date = December 1960 | pmid = 16748851 | pmc = 1205057 | doi = 10.1042/bj0770459 }}
* {{cite journal | vauthors = Fujioka M | title = Purification and properties of serine hydroxymethylase from soluble and mitochondrial fractions of rabbit liver | journal = Biochimica et Biophysica Acta (BBA) - Enzymology | volume = 185 | issue = 2 | pages = 338–349 | date = 1969 | pmid = 5808700 | doi = 10.1016/0005-2744(69)90427-6 }}
* {{cite journal | vauthors = Kumagai H, Nagate T, Yoshida H, Yamada H | title = Threonine aldolase from Candida humicola. II. Purification, crystallization and properties | journal = Biochimica et Biophysica Acta (BBA) - Enzymology | volume = 258 | issue = 3 | pages = 779–790 | date = March 1972 | pmid = 5017702 | doi = 10.1016/0005-2744(72)90179-9 }}
* {{cite journal | vauthors = Schirch L, Gross T | title = Serine transhydroxymethylase. Identification as the threonine and allothreonine aldolases | journal = The Journal of Biological Chemistry | volume = 243 | issue = 21 | pages = 5651–5655 | date = November 1968 | doi = 10.1016/S0021-9258(18)91916-2 | pmid = 5699057 | doi-access = free }}
* {{cite journal | vauthors = Schirch L, Quashnock J | title = Evidence that tetrahydrofolate does not bind to serine hydroxymethyltransferase with positive homotropic cooperativity | journal = The Journal of Biological Chemistry | volume = 256 | issue = 12 | pages = 6245–6249 | date = June 1981 | doi = 10.1016/S0021-9258(19)69154-4 | pmid = 6787050 | doi-access = free }}
* {{cite journal | vauthors = Quashnock JM, Chlebowski JF, Martinez-Carrion M, Schirch L | title = Serine hydroxymethyltransferase. 31P nuclear magnetic resonance study of the enzyme-bound pyridoxal 5'-phosphate | journal = The Journal of Biological Chemistry | volume = 258 | issue = 1 | pages = 503–507 | date = January 1983 | doi = 10.1016/S0021-9258(18)33284-8 | pmid = 6848517 | doi-access = free }}
{{refend}}

== External links ==
* {{MeSH name|Serine+Hydroxymethyltransferase}}

{{Amino acid metabolism enzymes}}
{{Metabolism of vitamins, coenzymes, and cofactors}}
{{Glycine receptor modulators}}
{{One carbon transferases}}
{{Enzymes}}
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[[Category:EC 2.1.2]]