1W68

Crystal Structure of Mouse Ribonucleotide Reductase Subunit R2 under Oxidizing Conditions. A Fully Occupied Dinuclear Iron Cluster.

Summary for 1W68

• Entry DOI: 10.2210/pdb1w68/pdb
• Related: 1AFT 1H0N 1H0O 1W69 1XSM
• Descriptor: RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE M2 CHAIN, MU-OXO-DIIRON (3 entities in total)
• Functional Keywords: reductase, ribonucleotide reductase, dna replication, diiron oxygen protein, tyrosyl radical, metal-binding, oxidoreductase
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Cytoplasm: P11157
• Total number of polymer chains: 1
• Total formula weight: 45277.24

Authors

Karlsen, S.,Strand, K.R.,Kolberg, M.,Rohr, A.K.,Gorbitz, C.H.,Andersson, K.K. (deposition date: 2004-08-16, release date: 2004-08-26, Last modification date: 2023-12-13)

Primary citation

Strand, K.R.,Karlsen, S.,Kolberg, M.,Rohr, A.K.,Gorbitz, C.H.,Andersson, K.K.
Crystal Structural Studies of Changes in the Native Dinuclear Iron Center of Ribonucleotide Reductase Protein R2 from Mouse
J.Biol.Chem., 279:46794-, 2004

PubMed Abstract: Class I ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleotides in mammals and many other organisms. The RNR subunit R2 contains a dinuclear iron center, which in its diferrous form spontaneously reacts with O2, forming a mu-oxo-bridged diferric cluster and a stable tyrosyl radical. Here, we present the first crystal structures of R2 from mouse with its native dinuclear iron center, both under reducing and oxidizing conditions. In one structure obtained under reducing conditions, the iron-bridging ligand Glu-267 adopts the mu-(eta1,eta2) coordination mode, which has previously been related to O2 activation, and an acetate ion from the soaking solution is observed where O2 has been proposed to bind the iron. The structure of mouse R2 under oxidizing conditions resembles the nonradical diferric R2 from Escherichia coli, with the exception of the coordination of water and Asp-139 to Fe1. There are also additional water molecules near the tyrosyl radical site, as suggested by previous spectroscopic studies. Since no crystal structure of the active radical form has been reported, we propose models for the movement of waters and/or tyrosyl radical site when diferric R2 is oxidized to the radical form, in agreement with our previous ENDOR study. Compared with E. coli R2, two conserved phenylalanine residues in the hydrophobic environment around the diiron center have opposing rotameric conformations, and the carboxylate ligands of the diiron center in mouse R2 appear more flexible. Together, this might contribute to the lower affinity and cooperative binding of iron in mouse R2.

PubMed: 15322079
DOI: 10.1074/JBC.M407346200

Experimental method

X-RAY DIFFRACTION (2.2 Å)