Cloning, expression, activity and folding studies of serine hydroxymethyltransferase: a target enzyme for cancer chemotherapy.
All the members of pyridoxal-5'-phosphate-dependent enzymes are involved in the metabolism of amino acids. The sequence homology studies further divide this family into three distinct groups. A fine scrutiny of the reactions catalyzed by these enzymes shows their regio specificity; they have been considered as the largest group of enzymes having tendency to affect the valency of the same carbon atom that carries the amino group forming an amine linkage with the coenzyme. Thus, this group was named 'alpha-class of enzymes'. Serine hydroxymethyltransferase (SHMT) is a member of this alpha-class; it reversibly catalyses the conversion of serine into glycine while the hydroxymethyl group is transferred to 5,6,7,8-tetrahydrofolate. The resultant compound is the sole precursor of purine biosynthesis. Henceforth, this enzyme greatly affects nucleic acid biosynthesis in all the organisms. It is obvious that SHMT plays an indispensable role in nucleic acid biosynthesis; therefore, designing and developing a repressor/inhibitor of the SHMT gene/protein may resolve the problem of drug resistance to cancer chemotherapy. SHMT has been widely studied in many living systems (e.g. Escherichia coli, humans, sheep, rabbits, Trypanosoma, Arabidopsis, peas, tobacco) in terms of its structure, cloning, expression, purification and folding patterns. Such studies have enabled one to assess the pattern of overall kinetic and activity behaviour of the enzyme, which may further help in developing a suitable cancer therapeutic molecule.
Agrawal
Shipra
S
Department of Biotechnology, Institute of Engineering and Technology, Lucknow, India.
Kumar
Ajay
A
Srivastava
Vivek
V
Mishra
B N
BN
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D012696:Glycine Hydroxymethyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D017510:Protein Folding; D011817:Rabbits
D004791:Enzyme Inhibitors; D012696:Glycine Hydroxymethyltransferase