A multisubstrate adduct inhibitor of AICAR transformylase

Journal of Medicinal Chemistry

Volumn 42, Issue 18, 1999, Pages 3421-3424

  Wall, Mark ^a   Shim, Jae Hoon ^a   Benkovic, Stephen J ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; ANTINEOPLASTIC AGENT; PHOSPHORIBOSYLAMINOIMIDAZOLECARBOXAMIDE FORMYLTRANSFERASE; PHOSPHORIBOSYLAMINOIMIDAZOLECARBOXAMIDE FORMYLTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG;

DRUG MECHANISM; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; ENZYME STRUCTURE; LETTER; PURINE SYNTHESIS;

ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; ENZYME INHIBITORS; FLUORESCENCE; GLUTAMIC ACID; HYDROXYMETHYL AND FORMYL TRANSFERASES; MULTIENZYME COMPLEXES; NUCLEOTIDE DEAMINASES; PHOSPHORIBOSYLAMINOIMIDAZOLECARBOXAMIDE FORMYLTRANSFERASE; PROTEIN BINDING; PTERINS; RIBONUCLEOTIDES; SUBSTRATE SPECIFICITY;

EID: 0344563519     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990323+     Document Type: Letter

References (24)

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16. 2O over 30 min.
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18. Fluorescence titration assays were carried out at 25 °C, pH 7.5 in 33 mM HEPES buffer and 25 mM KCl. Enzyme was purified from E. coli BL21(DE3) containing a plasmid that codes a Histagged human purH cDNA. The concentration of β-DADF was determined by measuring the concentration of inorganic phosphate (Chen, P. S.; Toribara, T. Y.; Warner, H. Microdetermination of phosphorus. Anal. Chem. 1956, 28, 1756-1758) in a solution of β-DADF that was hydrolyzed in 6 N HCl at 100 °C in a sealed tube for 12 h.
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20. 23
21. 4F at 298 nm in 33 mM Tris buffer containing 25 mM KCl at pH 7.5, 25 °C. Although β-DADF is a potent inhibitor of AICAR Tfase, its therapeutic potential may be limited due to its anionic nature, which most likely prohibits transport across biological membranes.
22. 4F and 25 μM AICAR).
23. Rayl, E. A.; Moroson, B. A.; Beardsley, G. P. The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase cloning, sequencing, expression, purification, kinetic analysis, and domain mapping. J. Biol. Chem. 1996, 271, 2225-2233.
24. IMP cyclase (10 nM) was assayed by following the conversion of 5-formyl-AICAR to IMP at 248 nm in 33 mM Tris buffer containing 25 mM KCl, pH 7.5, 25 °C. Concentrations of 10 μM β-DADF had no effect on the rate of IMP production.