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Bifunctional purine biosynthesis protein ATIC

Definition:

Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis. Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization.

References:

[1]. Karen G Bulock, et al. The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling. J Biol Chem. 2002 Jun 21;277(25):22168-74. [Content Brief]

[2]. Martial Boutchueng-Djidjou, et al. The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) plays a central role in insulin signaling and the Golgi/endosomes protein network. Mol Cell Proteomics. 2015 Apr;14(4):1079-92. [Content Brief]

[3]. M Wall, et al. Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding and catalysis. Biochemistry. 2000 Sep 19;39(37):11303-11. [Content Brief]

[4]. T Sugita, et al. Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase. J Biochem. 1997 Aug;122(2):309-13. [Content Brief]

[5]. James M Vergis, et al. Catalytic mechanism of the cyclohydrolase activity of human aminoimidazole carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase. Biochemistry. 2004 Feb 10;43(5):1184-92. [Content Brief]

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