3o0o

Thermotoga maritima Ribonucleotide Reductase, NrdJ, in complex with dTTP, GDP and Adenosylcobalamin

spinqualitylabelsall models 3o0o, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o0o is a 2 chain structure with sequence from Thermotoga maritima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 5AD, GDP, MG, TTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O33839_THEMT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Class II ribonucleotide reductases (RNR) catalyse the formation of an essential thiyl radical by homolytic cleavage of the Co-C bond in their adenosylcobalamin (AdoCbl) cofactor. Several mechanisms for the dramatic acceleration of Co-C bond cleavage in AdoCbl-dependent enzymes have been advanced, but no consensus yet exists. We present the structure of the class II RNR from Thermotoga maritima in three complexes: 1) with allosteric effector dTTP, substrate GDP and AdoCbl; 2) with dTTP and AdoCbl; 3) with dTTP, GDP and adenosine. Comparison of these structures gives the deepest structural insights so far into the mechanism of radical generation and transfer for AdoCbl-dependent RNR. AdoCbl binds to the active site pocket, shielding the substrate, transient 5'-deoxyadenosyl radical and nascent thiyl radical from solution. The e-propionamide side chain of AdoCbl forms hydrogen bonds directly to the alpha-phosphate group of the substrate. This interaction appears to cause a "locking-in" of the cofactor, and it is the first observation of a direct cofactor-substrate interaction in an AdoCbl-dependent enzyme. The structures support an ordered sequential reaction mechanism with release or relaxation of AdoCbl on each catalytic cycle. A conformational change of the AdoCbl adenosyl ribose is required to allow hydrogen transfer to the catalytic thiol group. Previously proposed mechanisms for radical transfer in B12-dependent enzymes cannot fully explain the mechanism in class II RNR, suggesting that it may form a separate class that differs from the well-characterised eliminases and mutases. Structural basis for adenosylcobalamin activation in AdoCbl-dependent ribonucleotide reductases.,Larsson KM, Logan DT, Nordlund P ACS Chem Biol. 2010 Jul 30. PMID:20672854 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonucleotide reductase 3D structures

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