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Target intelligence / Profile preview
Serine hydroxymethyltransferase 1 (SHMT1)
- Target
- SHMT1
- Molecular classification
- Enzyme, Pyridoxal 5’-phosphate-dependent enzyme, Aminotransferase superfamily
01
Overview
Serine hydroxymethyltransferase 1 (SHMT1) is a cytosolic, pyridoxal 5’-phosphate-dependent enzyme that catalyzes the reversible interconversion of serine and glycine, transferring a one-carbon unit to tetrahydrofolate (THF) to produce 5,10-methylenetetrahydrofolate, a central metabolite for nucleotide and methyl group biosynthesis[1][2][3][4]. It supports DNA synthesis, cell proliferation, and methylation reactions, and is a critical node in the folate cycle, making it a key target for anticancer and antimicrobial drug discovery[1][3].
- Other names
- Serine hydroxymethyltransferaseSHMTCytosolic serine hydroxymethyltransferaseGlyA (bacterial)
02
Mechanism of action
Inhibition of serine-to-glycine conversion and one-carbon donation restricts nucleotide synthesis and DNA replication, particularly in rapidly dividing cells[1][3].
03
Biological functions
One-carbon metabolismAmino acid metabolism (serine/glycine interconversion)Nucleotide synthesis (purine, thymidylate biosynthesis)Methylation reactions support (via S-adenosylmethionine production)
04
Disease associations
CancerOther (implicated in cell proliferation and potential antimicrobial target)
05
Safety considerations
Inhibition may impair normal rapidly dividing cells (e.g., bone marrow, gut epithelium)Potential folate cycle disruption, leading to toxicity similar to antifolate therapies
06
Interacting drugs
SHMT inhibitors (experimental, e.g., SHIN1, SHIN2)
1 more in the full profile.
07
Biomarkers
SHMT1 expression levels (potential biomarker in proliferative disorders, especially some cancers[3])5,10-methylenetetrahydrofolate (functional marker)
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