Hydrogen bonding and π–π stacking in hexaaquairon(II) bis(4′,7-dimethoxyisoflavone-3′-sulfonate) octahydrate

Zhang, Zunting; Cheng, Xin-Li

doi:10.1107/s0108270105036218

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…Carboxylate-derived Fe–O distances have a similar range but depend on the binding mode of the carboxylate ligand (i.e., monodentate vs bidentate or terminal vs bridging). Additionally, in synthetic iron(II) complexes, Fe II –OH 2 distances can range from 2.04 to 2.16 Å, consistent with this assignment. − The Fe–O/N scatterer at 1.97 Å is assigned to the hydroxo bridge between the metal centers, as synthetic (μ-hydroxo)diferrous complexes have Fe II –μ-OH distances as short as 1.97 Å. − This assignment would agree with the single atom bridge observed in the crystal structure of WT R and give rise to a diiron(II) active site with an overall neutral charge. Mössbauer studies of WT R reveal a diiron(II) center with weak antiferromagnetic coupling ( J ∼ 12 cm –1 ) .…”

Section: Resultssupporting

confidence: 72%

A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme β-Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase

Jasniewski

Knoot

Lipscomb³

et al. 2016

Biochemistry

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The first step in the nonribosomal peptide synthetase (NRPS)-based biosynthesis of chloramphenicol is the β-hydroxylation of the precursor L-para-aminophenylalanine (L-PAPA) catalyzed by the monooxygenase CmlA. The active site of CmlA contains a dinuclear iron cluster which is reduced to the diferrous state (WT R ) to initiate O 2 activation. However, rapid O 2 activation only occurs when WT R is bound to CmlP, the NRPS to which L-PAPA is covalently attached. Here the X-ray crystal structure of WT R is reported, which is very similar to that of the as-isolated diferric enzyme in which the irons are coordinately saturated. X-ray absorption spectroscopy is used to investigate the WT R cluster ligand structure as well as the structures of WT R in complex with a functional CmlP variant (CmlP AT ) with and without L-PAPA attached. It is found that formation of the active WT R -CmlP AT~L -PAPA complex converts at least one iron of the cluster from six-to five-coordinate by changing a bidentately bound amino acid carboxylate to monodentate on Fe1. The only bidentate carboxylate in the structure of WT R is E377. The crystal structure of the CmlA variant E377D shows only monodentate carboxylate coordination. Reduced E377D reacts rapidly with O 2 in the presence or absence of CmlP AT~L -PAPA, showing loss of regulation. However this variant fails to catalyze hydroxylation, suggesting that E377 has the dual role of coupling regulation of O 2 reactivity with juxtaposition of the substrate and the reactive oxygen species. The carboxylate shift in response to substrate binding represents a novel regulatory strategy for oxygen activation in diiron oxygenases. Graphical abstract * Corresponding Authors

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Section: Resultssupporting

confidence: 72%

A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme β-Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase

Jasniewski

Knoot

Lipscomb³

et al. 2016

Biochemistry

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X-ray absorption spectroscopic characterization of the diferric-peroxo intermediate of human deoxyhypusine hydroxylase in the presence of its substrate eIF5a

Jasniewski

Engstrom

et al. 2016

J Biol Inorg Chem

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Human deoxyhypusine hydroxylase (hDOHH) is an enzyme that is involved in the critical post-translational modification of the eukaryotic translation initiation factor 5A (eIF5A). Following the conversion of a lysine residue on eIF5A to deoxyhypusine (Dhp) by deoxyhypusine synthase, hDOHH hydroxylates Dhp to yield the unusual amino acid residue hypusine (Hpu), a modification that is essential for eIF5A to promote peptide synthesis at the ribosome, among other functions. Purification of hDOHH overexpressed in E. coli affords enzyme that is blue in color, a feature that has been associated with the presence of a peroxo-bridged diiron(III) active site. To gain further insight into the nature of the diiron site and how it may change as hDOHH goes through the catalytic cycle, we have conducted X-ray absorption spectroscopic studies of hDOHH on five samples that represent different species along its reaction pathway. Structural analysis of each species has been carried out, starting with the reduced diferrous state, proceeding through its O2 adduct, and ending with a diferric decay product. Our results show that the Fe•••Fe distances found for the five samples fall within a narrow range of 3.4–3.5 Å, suggesting that hDOHH has a fairly constrained active site. This pattern differs significantly from what has been associated with canonical dioxygen activating nonheme diiron enzymes such as soluble methane monooxygenase and Class 1A ribonucleotide reductases, for which the Fe•••Fe distance can change by as much as 1 Å during the redox cycle. These results suggest that the O2 activation mechanism for hDOHH deviates somewhat from that associated with the canonical nonheme diiron enzymes, opening the door to new mechanistic possibilities for this intriguing family of enzymes.

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Hydrogen bonding and π–π stacking in hexaaquairon(II) bis(4′,7-dimethoxyisoflavone-3′-sulfonate) octahydrate

Cited by 2 publications

References 6 publications

A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme β-Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase

A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme β-Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase

X-ray absorption spectroscopic characterization of the diferric-peroxo intermediate of human deoxyhypusine hydroxylase in the presence of its substrate eIF5a

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