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The gateway to guanine nucleotides: Allosteric regulation of IMP dehydrogenases.

ABSTRACT: Inosine 5'-monophosphate dehydrogenase (IMPDH) is an evolutionarily conserved enzyme that mediates the first committed step in de novo guanine nucleotide biosynthetic pathway. It is an essential enzyme in purine nucleotide biosynthesis that modulates the metabolic flux at the branch point between adenine and guanine nucleotides. IMPDH plays key roles in cell homeostasis, proliferation, and the immune response, and is the cellular target of several drugs that are widely used for antiviral and immunosuppressive chemotherapy. IMPDH enzyme is tightly regulated at multiple levels, from transcriptional control to allosteric modulation, enzyme filamentation, and posttranslational modifications. Herein, we review recent developments in our understanding of the mechanisms of IMPDH regulation, including all layers of allosteric control that fine-tune the enzyme activity.

SUBMITTER: Buey RM

PROVIDER: S-EPMC9375230 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The gateway to guanine nucleotides: Allosteric regulation of IMP dehydrogenases.

Buey Rubén M RM Fernández-Justel David D Jiménez Alberto A Revuelta José L JL

Protein science : a publication of the Protein Society 20220901 9

Inosine 5'-monophosphate dehydrogenase (IMPDH) is an evolutionarily conserved enzyme that mediates the first committed step in de novo guanine nucleotide biosynthetic pathway. It is an essential enzyme in purine nucleotide biosynthesis that modulates the metabolic flux at the branch point between adenine and guanine nucleotides. IMPDH plays key roles in cell homeostasis, proliferation, and the immune response, and is the cellular target of several drugs that are widely used for antiviral and imm ...[more]

PMID: 36040265

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