The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs) family of secreted metalloproteinases plays essential roles in extracellular matrix remodeling. ADAMTS-5 contributes to cartilage degradation, cleaving proteoglycans such as aggrecan and versican, and being involved in both physiological tissue turnover and pathological processes such as osteoarthritis and atherosclerosis. Although structural insights into its catalytic domain have informed inhibitor development, the role of ancillary domains, particularly the spacer domain, in substrate recognition and specificity remains underexplored. Here, we report the crystal structure of a segment of human ADAMTS-5 encompassing the C-terminal portion of the cysteine-rich domain and the spacer domain (residues 694-876). This structure reveals critical features of the spacer domain, including the hypervariable loops that function as exosites essential for the binding of aggrecan and versican. Our findings provide new structural insights into the molecular determinants of the substrate specificity of ADAMTS-5 and underscore the spacer domain as a promising target for the development of selective inhibitors.

Microbial transport systems of organic sulfur compounds: Diversity and implications for biocatalysis, healthcare, and environmental biotechnology.

Phylogenetic and structural analyses reveal Cdc2-like kinases (CLKs) as ancient regulators of thermosensitive splicing.

A smartphone-assisted dual-mode sensor based on GN-CDs for sensitive and portable detection of α-glucosidase.

Structural and functional analyses of Pcal_1233, a highly thermoactive glycerate 2-kinase from Pyrobaculum calidifontis.

Mononuclear iron(iv)-oxo, iron(iv)-imido and iron(iv)-nitrido complexes are common catalytic cycle intermediates in enzymes, where the metal is typically linked to the protein through cysteinate or histidine sidechains. Enzymatic high-valent iron(iv)-imido and -nitrido intermediates have never been trapped and characterized; hence, there is uncertainty regarding their structure and function. Using biomimetic models, we have synthesized a novel N4S ligated iron(iv)-imido species as a faithful mimic of a corresponding intermediate in nitrogenase. The complex was characterized with a range of techniques, including UV-vis absorption spectroscopy, electrospray ionization mass spectrometry, resonance Raman spectroscopy and XANES and EXAFS methodologies. A comprehensive investigation combining reactivity studies and computational analysis compares the oxidative reactivity and chemical properties of the iron(iv)-imido complex with those of its oxo-analogue. Although the iron(iv)-oxo species is, in general, more reactive than its iron(iv)-tosylimido counterpart, the reverse trend is observed for the oxidation of specific para-substituted thioanisole substrates. Furthermore, an equatorial sulfur group in the ligand framework is seen to enhance the reactivity of thioanisole sulfoxidation. These studies show that high-valent metal-imido groups can be as powerful oxidants as iron(iv)-oxo entities in atom/group transfer reactions.

Microglial phagoptosis in development, health, and disease.

The protein kinase C (PKC) family comprises enzyme kinases that regulate cell survival, metabolism, and proliferation. PKC isotypes (PKCs) phosphorylate specific downstream substrates, thereby controlling critical steps in both mitotic and meiotic cell division. Throughout the cell cycle, PKCs orchestrate essential processes, such as chromosome segregation, recombination, and cell cycle progression. In vertebrates, PKCs play essential roles in oogenesis and the early stages of embryo development. Disruption of PKC signaling in mammalian oocytes can lead to errors in chromosome segregation and induce meiotic arrest. Therefore, investigating PKC function in meiosis is crucial for advancing fundamental biological research and for developing new approaches to infertility treatment.

NRAMP family in plants: Contribution to cadmium accumulation.

Echinacea purpurea hydroxycinnamoyl-CoA:tartaric acid hydroxycinnamoyl transferase (EpHTT) is a cytosolic BAHD acyltransferase that catalyzes the transfer of caffeoyl groups to tartaric acid, a key step in chicoric acid biosynthesis. Understanding the structure of EpHTT is essential to elucidate the molecular basis of substrate recognition and catalytic specificity. Here, we report the crystal structure of apo-form EpHTT at 2.38 Å resolution, revealing a compact, globular architecture typical of the BAHD superfamily. The enzyme adopts a two-domain fold with conserved HXXXD and DFGWG motifs, forming a V-shaped catalytic cleft characteristic of BAHD acyltransferases. Structural comparison with homologous hydroxycinnamoyl transferase enzymes shows high conservation of the overall fold, while EpHTT exhibits unique adaptations that confer specificity for tartaric acid. These results provide a molecular framework for understanding the function and substrate specificity of HTT, offering insights for the metabolic engineering of chicoric acid production.

Production of polyhydroxyalkanoates by Halomonas sp. HG01, a halophilic bacterium from northern Peru, using various carbon sources: metabolic and genomic analysis.

Identification and functional characterization of a regioselective O-methyltransferase involved in physcion biosynthesis in Polygonum cuspidatum.

Decoding class II PI3K signaling: From membrane identity to human disease.

Anti-biofilm efficiency and substrate specificity of recombinantly produced human paraoxonases.

Identification of a thermostable GH6 family cellulase from chaetomium thermophilum exhibiting high cellobiose and ionic liquid tolerance.

Biochemical characterization of recombinant Aspergillus niger GZUF36 acetylcholinesterase for pesticide monitoring.

Engineering chimeric polyhydroxyalkanoate synthases for enhanced copolymerization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate): A promising biotechnological approach.

Organic anion transporter 1 (OAT1) is a mechanism for uptake of mercuric-cyanide complexes into proximal tubular cells.

How evolution shaped the structure of steroidogenic cytochrome P450 11A.

Impact of 6-purine modifications on the ribose substrate selectivity of pyrimidine nucleoside phosphorylase (PyNP) in base exchange reactions.