Dogfish M4 lactate dehydrogenase: reversible inactivation by pyridoxal 5''-phosphate and complete protection in complexes that mimic the active ternary complex.

Dogfish M4 lactate dehydrogenase, like the corresponding pig enzyme, is inactivated by pyridoxal 5'-phosphate through modification of a single essential lysine residue. The activity is completely protected in the complexes E-NAD+-oxalate, E-NADH-oxamate and E-(NAD+-pyruvate adduct), but only partially protected in E-NAD+, E-NADH, E-NAD+-oxamate and E-NADH-oxalate.     

Anotia, facial paralysis, heart abnormalities: specific triad or variant of Goldenhar syndrome?

A girl was born with anotia, facial palsy and cardiac malformations. Her case is compared with three other similar ones described in the literature, and the question is raised as to whether this is a new clinical entity or represents a variation of Goldenhar syndrome.     

Estimation of binding parameters of enzyme-ligand complex from fluorometric data by a curve fitting procedure: seryl-tRNA synthetase-tRNA Ser complex

A curve fitting procedure for the determination of the association constant, number of binding sites, and theoretical titration end point of an enzyme-ligand interaction monitored by fluorescence quenching titration is described and compared with classical graphical evaluation processes.     

A novel bufadienolide synthesis

A simple two-step synthesis of bufadienolides is reported. It consists in the addition of the dimethyl acetal of chloroketene to a steroidal 20-methylene 21-aldehyde and in the treatment of the resulting 2,2-dimethoxy 3-chloro 2,3-dihydropyran with sodium methoxide in dimethylsulfoxide. This method is exemplified by the synthesis of 3β-hydroxy-5α,14α-bufadienolide from 3β-acetoxy-20-methylene-5α-pregnan-21-al, prepared from 3β-acetoxy-5α-androstan-17-one. The new procedure represents the most efficient bufadienolide synthesis yet known.     

Enhancement of heat sensitivity and modification of repair of potentially lethal heat damage in plateau-phase cultures of mammalian cells by diethyldithiocarbamate

Diethyldithiocarbamate (DDC) is active both in vivo and in vitro in reducing the levels of enzymes such as superoxide dismutase (SOD) and glutathione peroxidase whose role in respiring cells is to remove toxic superoxide radicals and organic hydroperoxides. Although DDC, a copper-chelating agent, has been used to treat benign diseases, its potential as a heat sensitizer has not been fully explored. We have recently shown that the presence of 10(-3) M DDC for 2 hr causes a threefold reduction in the level of SOD in plateau-phase cultures of mammalian cells. At this concentration, the drug causes minimal toxicity but markedly affects both the shoulder and the slope of the heat survival curves. To explore another pathway of DDC sensitization, other than through reduced levels of SOD, we examined the repair of potentially lethal damage with and without DDC following exposure for 1 hr and 40 min at 43 degrees C. The repair, which progressed with a T 1/2 of about 10 hr, in either full medium or Hank's balanced salt solution (HBSS), in the absence of DDC, was completely blocked when DDC was added to the monolayers on completion of the heat exposure. DDC, in view of its ability to potentiate the effects of heat, is a potentially useful drug that could be used in an adjunctive setting with clinical hyperthermia.     

Visualizing biomolecular electrostatics in virtual reality with UnityMol‐APBS

Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson‐Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two‐dimensional external molecular visualization software. This process has inherent limitations: visualization of three‐dimensional objects using a two‐dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol‐APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience.