DETERMINING ALLOSTERIC REGULATION OF RIBONUCLEOTIDE REDUCTASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in production of the pool of deoxyribonucleotides necessary for DNA replication. Crucial for rapidly proliferating cells, RNR is a successful target for anti-HSV and anticancer drugs. Though there are crystal structures of the Rnr2p+Rnr4p heterodimer and the recently solved Rnr1p structure from our lab, the structural details of the assembly of the yeast RNR complex and the oligomerization state of Rn1p is not known. The overall goal of our experiments is to characterize interactions between Rnr1p and Rnr2p+Rnr4p complex, and to determine how Rnr1p undergo nucleotide dependent oligomerization. We will also extend this work to study the dNTP dependent oligomerization of the human RNR system. During this proposal we will perform a series of small-angle x-ray scattering experiments to provide a structural model for the higher-order RNR complex.