Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation

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   Fig. 1.

   Structure of Rnr1. (A) The dimer of apo Rnr1. Rnr1 monomers are yellow and green; dGTP (violet) and ADP (blue) from the cognate complex are shown in the specificity and catalytic sites. The three-helix insert and C-terminal insert are red and blue, respectively. (B) 1.0 σ 2F_o–F_c electron density for effector (blue density), loop 2 (red density), and substrate (green density) for the dGTP–ADP complex.

   
   
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   Fig. 2.

   The catalytic site. (A) A schematic of ribose in the catalytic site of the dGTP–ADP complex. Carbon is yellow, oxygen red, nitrogen blue, and sulfur green. (B–E) Substrate binding (loop 2 is shown on the right). Secondary structure: dGTP–ADP, magenta; TTP–GDP, blue; AMPPNP–CDP, orange; and AMPPNP–UDP, yellow. Interacting atoms are colored as above, except phosphate, magenta; substrate carbons, cyan; protein Cα carbons, as in secondary structure. (B) Stereoview of dGTP–ADP. (C) Stereoview of TTP–GDP. (D) Stereoview of AMPPNP–CDP. (E) Stereoview of AMPPNP–UDP.

   
   
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   Fig. 3.

   Specificity-site interactions. (A) Loop-2 rearrangements. Substrate (Left) and loop 2 and effector (Right) are shown for AMPPNP–UDP (yellow). Loop 2 is shown for apo (black), AMPPNP only (gray), and AMPPNP–CDP (orange). P294 is shown for apo and AMPPNP only. Q288 and R293 are shown for AMPPNP–CDP and AMPPNP–UDP. Cα spheres are shown for Q288, R293, and P294 in all structures. (B–E) Specificity effector binding. Colors of secondary structure cartoons are as in Fig. 2. Loop-1 carbons are yellow; Loop-2 carbons, light blue; other interacting atoms are colored as in Fig. 2, except effector carbons, which are green. (B) Stereoview of dGTP–ADP. (C) Stereoview of TTP–GDP. (D) Stereoview of AMPPNP–CDP. (E) Stereoview of AMPPNP–UDP.