SHMT1 Human

SHMT1 is a pyridoxal phosphate (PLP)-dependent enzyme, which means it requires PLP (a form of vitamin B6) as a cofactor to function properly . The enzyme catalyzes the reversible conversion of L-serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-CH2-THF) . This reaction is essential as it provides the largest part of the one-carbon units available to the cell, which are critical for various biosynthetic processes, including nucleotide synthesis .

The structure of SHMT1 is highly conserved across different species. In humans, SHMT1 exists as a homotetramer, meaning it forms a complex of four identical subunits . Each monomer of SHMT1 can be subdivided into three domains: an N-terminus “arm,” a “large” domain, and a “small” domain . The N-terminus arm is responsible for maintaining the tight interaction between two monomers, while the large domain contains the PLP binding site . The tetrameric form of SHMT1 is stabilized by histidine residues that engage in stacking interactions at the center of the complex .

SHMT1 plays a pivotal role in nucleotide biosynthesis, making it an attractive target for cancer chemotherapy . Elevated SHMT activity is often observed in rapidly proliferating cells, such as tumor cells, due to the increased demand for DNA synthesis . The enzyme’s central role in the thymidylate synthase metabolic cycle further underscores its importance in cellular metabolism .

Recombinant SHMT1 refers to the enzyme produced through recombinant DNA technology, typically expressed in systems such as Escherichia coli . This recombinant form is used extensively in research to study the enzyme’s structure, function, and potential as a therapeutic target .