Inter-lobe Motions Allosterically Regulate the Structure and Function of EGFR Kinase.

Protein kinases play important roles in cellular signaling and have been one of the best-studied drug targets. The kinase domain of epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that has been extensively studied for cancer drug discovery and for understanding the unique activation mechanism by dimerization. Here, we analyzed all available 206 crystal structures of the EGFR kinase and the dynamics observed in molecular simulations to identify how these structures are determined.

Different mechanisms between copper and iron in catecholamines-mediated oxidative DNA damage and disruption of gene expression in vitro.

Catechols produce reactive oxygen species (ROS) and induce oxidative DNA damage through reduction-oxidation reactions with metals such as copper. Here, we examined oxidative DNA damage by neurotransmitter catecholamines in the presence of copper or iron and evaluated the effects of this damage on gene expression in vitro. Dopamine induced strand breaks and base oxidation in calf thymus DNA in the presence of Cu(II) or Fe(III)-NTA (nitrilotriacetic acid).

Carbonyl side-chain of catechol compounds is a key structure for the suppression of copper-associated oxidative DNA damage in vitro.

Catechol is possibly carcinogenic to humans (International Agency for Research on Cancer, IARC). The key mechanism could include its oxidative DNA-damaging effect in combination with reductive-oxidative metals like Cu. We found that DNA damage was suppressed by introducing an α-carbonyl group to catechol at C4-position to produce carbonyl catechols.

Effects of redecoration of a hospital isolation room with natural materials on stress levels of denizens in cold season.

We investigated the effects of redecoration of a hospital isolation room with natural materials on thermoregulatory, cardiovascular and hormonal parameters of healthy subjects staying in the room. Two isolation rooms with almost bilaterally-symmetrical arrangements were used. One room (RD) was redecorated with wood paneling and Japanese paper, while the other (CN) was unchanged (with concrete walls).