1w69
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Class I ribonucleotide reductase (RNR) catalyzes the de novo synthesis of | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Ribonucleoside-diphosphate reductase]] | [[Category: Ribonucleoside-diphosphate reductase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Andersson, K | + | [[Category: Andersson, K K.]] |
| - | [[Category: Gorbitz, C | + | [[Category: Gorbitz, C H.]] |
[[Category: Karlsen, S.]] | [[Category: Karlsen, S.]] | ||
[[Category: Kolberg, M.]] | [[Category: Kolberg, M.]] | ||
| - | [[Category: Rohr, A | + | [[Category: Rohr, A K.]] |
| - | [[Category: Strand, K | + | [[Category: Strand, K R.]] |
[[Category: ACY]] | [[Category: ACY]] | ||
[[Category: FE2]] | [[Category: FE2]] | ||
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[[Category: tyrosyl radical]] | [[Category: tyrosyl radical]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:53 2008'' |
Revision as of 13:40, 21 February 2008
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CRYSTAL STRUCTURE OF MOUSE RIBONUCLEOTIDE REDUCTASE SUBUNIT R2 UNDER REDUCING CONDITIONS. A FULLY OCCUPIED DINUCLEAR IRON CLUSTER AND BOUND ACETATE.
Overview
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.
About this Structure
1W69 is a Single protein structure of sequence from Mus musculus with and as ligands. Active as Ribonucleoside-diphosphate reductase, with EC number 1.17.4.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Crystal structural studies of changes in the native dinuclear iron center of ribonucleotide reductase protein R2 from mouse., Strand KR, Karlsen S, Kolberg M, Rohr AK, Gorbitz CH, Andersson KK, J Biol Chem. 2004 Nov 5;279(45):46794-801. Epub 2004 Aug 17. PMID:15322079
Page seeded by OCA on Thu Feb 21 15:40:53 2008
Categories: Mus musculus | Ribonucleoside-diphosphate reductase | Single protein | Andersson, K K. | Gorbitz, C H. | Karlsen, S. | Kolberg, M. | Rohr, A K. | Strand, K R. | ACY | FE2 | Diiron oxygen protein | Dna replication | Metal-binding | Oxidoreductase | Ribonucleotide reductase | Tyrosyl radical
