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5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase.
J Biol Chem. 1991 Jan 25; 266(3):1543-50.JB

Abstract

The interaction of the mono- and triglutamate forms of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate with serine hydroxymethyltransferase were determined by several methods. These methods included: determining dissociation constants by observing the absorbance at 502 nm of a ternary complex of the enzyme, glycine, and the folate compounds; determining inhibition constants from steady-state reactions; and determining the rate of formation and breakdown of the enzyme inhibitor complex by rapid reaction kinetics. Studies of the dissociation and inhibitor constants showed that both 5-methyltetrahydrofolate and 5-formyltetrahydrofolate have essentially the same affinity for the enzyme-glycine binary complex. However, rapid reaction and steady-state kinetic studies showed that the triglutamate form of 5-formyltetrahydrofolate both binds and is released much more slowly from the enzyme-glycine binary complex, compared with the triglutamate form of 5-methyltetrahydrofolate. The results also showed that only one rotamer of 5-formyltetrahydrofolate binds at the active site of serine hydroxymethyltransferase. The results are discussed in terms of the possible role of 5-formyltetrahydrofolate polyglutamates in regulation of one-carbon metabolism.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1988436

Citation

Stover, P, and V Schirch. "5-Formyltetrahydrofolate Polyglutamates Are Slow Tight Binding Inhibitors of Serine Hydroxymethyltransferase." The Journal of Biological Chemistry, vol. 266, no. 3, 1991, pp. 1543-50.
Stover P, Schirch V. 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase. J Biol Chem. 1991;266(3):1543-50.
Stover, P., & Schirch, V. (1991). 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase. The Journal of Biological Chemistry, 266(3), 1543-50.
Stover P, Schirch V. 5-Formyltetrahydrofolate Polyglutamates Are Slow Tight Binding Inhibitors of Serine Hydroxymethyltransferase. J Biol Chem. 1991 Jan 25;266(3):1543-50. PubMed PMID: 1988436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase. AU - Stover,P, AU - Schirch,V, PY - 1991/1/25/pubmed PY - 1991/1/25/medline PY - 1991/1/25/entrez SP - 1543 EP - 50 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 266 IS - 3 N2 - The interaction of the mono- and triglutamate forms of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate with serine hydroxymethyltransferase were determined by several methods. These methods included: determining dissociation constants by observing the absorbance at 502 nm of a ternary complex of the enzyme, glycine, and the folate compounds; determining inhibition constants from steady-state reactions; and determining the rate of formation and breakdown of the enzyme inhibitor complex by rapid reaction kinetics. Studies of the dissociation and inhibitor constants showed that both 5-methyltetrahydrofolate and 5-formyltetrahydrofolate have essentially the same affinity for the enzyme-glycine binary complex. However, rapid reaction and steady-state kinetic studies showed that the triglutamate form of 5-formyltetrahydrofolate both binds and is released much more slowly from the enzyme-glycine binary complex, compared with the triglutamate form of 5-methyltetrahydrofolate. The results also showed that only one rotamer of 5-formyltetrahydrofolate binds at the active site of serine hydroxymethyltransferase. The results are discussed in terms of the possible role of 5-formyltetrahydrofolate polyglutamates in regulation of one-carbon metabolism. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/1988436/5_Formyltetrahydrofolate_polyglutamates_are_slow_tight_binding_inhibitors_of_serine_hydroxymethyltransferase_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1988436 DB - PRIME DP - Unbound Medicine ER -