Collagen lysyl hydroxylases (LH1-3) are Fe2+- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 Å crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded β-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe2+. The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-binding site. Loss of Fe2+-binding disrupts the dimer. Dimer disruption and charge reversal in the cleft increase Km and reduce LH activity. Ectopic L230 expression in tumors promotes collagen cross-linking and metastasis. These insights suggest inhibitor targets for fibrosis and cancer.
Water use has been increasing globally by 1% per year, and recycling and re-use are critical issues compromised by the presence of pollutants. In this context, the design of novel materials and/or procedures for the large scale-removal of pollutants must be economically and environmentally feasible in order to be considered as part of the solution by emerging economies. We demonstrate that the cross-linking of biodegradable polysaccharides such as starch, dextrin, or dextrin and β-cyclodextrin with divinyl sulfone is an innovative strategy for synthesizing insoluble and eco-friendly sorbent polymers, including pSt, pDx and pCD-Dx. The evaluation of these polymers’ ability to remove ciprofloxacin (CIP), a prime example of antibiotic pollution, revealed that pSt, with a Kd of 1469 L/kg and a removal rate higher than 92%, is a favorable material. Its sorption is pH-dependent and enhanced at a mildly alkaline pH, allowing for the desorption (i.e., cleaning) and reuse of pSt through an environmentally friendly treatment with 20 mM AcONa pH 4.6. The facts that pSt (i) shows a high affinity for CIP even at high NaCl concentrations, (ii) can be obtained from affordable starting materials, and (iii) is synthesized and regenerated through organic, solvent-free procedures make pSt a novel sustainable material for inland water and seawater remediation, especially in less developed countries, due to its simplicity and low cost.
The 1.5 Å resolution crystal structure of DynU16, a protein identified in the dynemicin-biosynthetic gene cluster, is reported. The structure adopts a di-domain helix-grip fold with a uniquely positioned open cavity connecting the domains. The elongated dimensions of the cavity appear to be compatible with the geometry of a linear polyene, suggesting the involvement of DynU16 in the upstream steps of dynemicin biosynthesis.
The
use of a catalyst support for the design of nanoscale heterogeneous
catalysts based on cerium oxide offers vast possibilities for future
catalyst development, particularly with regard to an increased focus
on the use of renewable biogas and an emerging hydrogen economy. In
this study, zirconia-supported ceria catalysts were synthesized, activated
by using different thermochemical treatments, and characterized by
way of temperature-programmed reduction (TPR), oxygen storage capacity,
X-ray diffraction, electron microscopy, and luminescence spectroscopy
using Eu3+ as a spectroscopic probe. Through reduction–oxidation
pretreatment routines, reactive pyrochlore structures were created
at temperatures as low as 600 °C and identified through TPR and
electron microscopy experiments. A structural relationship and alignment
of the crystal planes is revealed in high-resolution scanning transmission
electron microscopy experiments through the digital diffraction patterns.
Low-temperature pretreatment induces the formation of reactive pyrochlore
domains under retention of the surface area of the catalyst system,
and no further morphological changes are detected. Furthermore, the
formation of pyrochlore domains achieved through severe reduction
and mild reoxidation (SRMO) treatments is reversible. Over multiple
alternating SRMO and severe reduction and severe reoxidation (SRSO)
treatments, europium spectroscopy and TPR results indicate that pyrochlore
structures are recreated over consecutive treatments, whenever the
mild oxidation step at 500 °C is the last treatment (SRMO, SRMO–SRSO–SRMO,
etc.).
In the originally published version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to also include support from the National Institutes of Health grant T32GM008280 to Sarah Alvarado.
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