The non-swapped monomeric structure of the arginine-binding protein from Thermotoga maritima.

Domain swapping is a widespread oligomerization process that is observed in a large variety of protein families. In the large superfamily of substrate-binding proteins, non-monomeric members have rarely been reported. The arginine-binding protein from Thermotoga maritima (TmArgBP), a protein endowed with a number of unusual properties, presents a domain-swapped structure in its dimeric native state in which the two polypeptide chains mutually exchange their C-terminal helices.

Structure-Activity Relationships of (l-Tyrosyl-l-tyrosine) Derivatives Binding to CYP121: Iodinated Analogues Promote Shift to High-Spin Adduct.

A series of analogues of (l-tyrosyl-l-tyrosine), the substrate of the enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto (l-tyrosyl-l-tyrosine) results in sub-μM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme Fe. The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds.

Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery.

Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437.