4hr4 | pdb_00004hr4

R2-like ligand-binding oxidase with anaerobically reconstituted metal cofactor

spinqualitylabelsall models 4hr4, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hr4 is a 1 chain structure with sequence from Geoka. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FE2, MN, PLM Related: 4hr0, 4hr5 Gene: GK2771 (GEOKA) Activity: Ribonucleoside-diphosphate reductase, with EC number 1.17.4.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding specificity arises remains poorly understood, especially in the case of metals with similar primary ligand preferences such as manganese and iron. The biochemical selection of manganese over iron presents a particularly intricate problem because manganese is generally present in cells at a lower concentration than iron, while also having a lower predicted complex stability according to the Irving-Williams series (Mn(II) < Fe(II) < Ni(II) < Co(II) < Cu(II) > Zn(II)). Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein ligands in both metal sites self-assembles from Mn(II) and Fe(II) in vitro, thus diverging from the Irving-Williams series without requiring auxiliary factors such as metallochaperones. Crystallographic, spectroscopic, and computational data demonstrate that one of the two metal sites preferentially binds Fe(II) over Mn(II) as expected, whereas the other site is nonspecific, binding equal amounts of both metals in the absence of oxygen. Oxygen exposure results in further accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least a two-step process governed by both the intrinsic metal specificity of the protein scaffold and additional effects exerted during oxygen binding or activation. We further show that the mixed-metal cofactor catalyzes a two-electron oxidation of the protein scaffold, yielding a tyrosine-valine ether cross-link. Theoretical modeling of the reaction by density functional theory suggests a multistep mechanism including a valyl radical intermediate. Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein.,Griese JJ, Roos K, Cox N, Shafaat HS, Branca RM, Lehtio J, Graslund A, Lubitz W, Siegbahn PE, Hogbom M Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17189-94. doi:, 10.1073/pnas.1304368110. Epub 2013 Oct 7. PMID:24101498 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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