The mononuclear molybdenum enzymes.
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ABSTRACT:
SUBMITTER: Hille R
PROVIDER: S-EPMC4080432 | biostudies-literature | 2014 Apr
REPOSITORIES: biostudies-literature
Publications
The mononuclear molybdenum enzymes.
Hille Russ R Hall James J Basu Partha P
Chemical reviews 20140128 7
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Project description:Recent progress in our understanding of the structural and catalytic properties of molybdenum-containing enzymes in eukaryotes is reviewed, along with aspects of the biosynthesis of the cofactor and its insertion into apoprotein.
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Project description:Superoxide (O(2)(-)) is a primary agent of intracellular oxidative stress. Genetic studies in many organisms have confirmed that excess O(2)(-) disrupts metabolism, but to date only a small family of [4Fe-4S] dehydratases have been identified as direct targets. This investigation reveals that in Escherichia coli O(2)(-) also poisons a broader cohort of non-redox enzymes that employ ferrous iron atoms as catalytic cofactors. These enzymes were inactivated by O(2)(-) both in vitro and in vivo. Although the enzymes are known targets of hydrogen peroxide, the outcome with O(2)(-) differs substantially. When purified enzymes were damaged by O(2)(-) in vitro, activity could be completely restored by iron addition, indicating that the O(2)(-) treatment generated an apoprotein without damaging the protein polypeptide. Superoxide stress inside cells caused the progressive mismetallation of these enzymes with zinc, which confers little activity. When O(2)(-) stress was terminated, cells gradually restored activity by extracting zinc from the proteins. The overloading of cells with zinc caused mismetallation even without O(2)(-) stress. These results support a model in which O(2)(-) repeatedly excises iron from these enzymes, allowing zinc to compete with iron for remetallation of their apoprotein forms. This action substantially expands the physiological imprint of O(2)(-) stress.
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Project description:We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.
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