title: The structural basis for the allosteric regulation of ribonucleotide reductase.
abstract: Ribonucleotide reductases (RRs) catalyze a crucial step of de novo DNA synthesis by converting ribonucleoside diphosphates to deoxyribonucleoside diphosphates. Tight control of the dNTP pool is essential for cellular homeostasis. The activity of the enzyme is tightly regulated at the S-phase by allosteric regulation. Recent structural studies by our group and others provided the molecular basis for understanding how RR recognizes substrates, how it interacts with chemotherapeutic agents, and how it is regulated by its allosteric regulators ATP and dATP. This review discusses the molecular basis of allosteric regulation and substrate recognition of RR, and particularly the discovery that subunit oligomerization is an important prerequisite step in enzyme inhibition.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Md Faiz
authors.initials: MF
authors.lastname: Ahmad
authors.forename: Chris G
authors.initials: CG
authors.lastname: Dealwis
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D021122:Protein Subunits; D012264:Ribonucleotide Reductases