Antagonistic Effects of Point Mutations on Charge Recombination and a New View of Primary Charge Separation in Photosynthetic Proteins.

Light-induced electron-transfer reactions were investigated in wild-type and three mutant Rhodobacter sphaeroides reaction centers with the secondary electron acceptor (ubiquinone QA) either removed or permanently reduced. Under such conditions, charge separation between the primary electron donor (bacteriochlorophyll dimer, P) and the electron acceptor (bacteriopheophytin, HA) was followed by P+HA- → PHA charge recombination. Two reaction centers were used that had different single amino-acid mutations that brought about either a 3-fold acceleration in charge recombination compared to that in the wild-type protein, or a 3-fold deceleration. In a third mutant in which the two single amino-acid mutations were combined, charge recombination was similar to that in the wild type. In all cases, data from transient absorption measurements were analyzed using similar models. The modeling included the energetic relaxation of the charge-separated states caused by protein dynamics and evidenced the appearance of an intermediate charge-separated state, P+BA-, with BA being the bacteriochlorophyll located between P and HA. In all cases, mixing of the states P+BA- and P+HA- was observed and explained in terms of electron delocalization over BA and HA. This delocalization, together with picosecond protein relaxation, underlies a new view of primary charge separation in photosynthesis.

Unified Model of Nanosecond Charge Recombination in Closed Reaction Centers from Rhodobacter sphaeroides: Role of Protein Polarization Dynamics.

Ongoing questions surround the influence of protein dynamics on rapid processes such as biological electron transfer. Such questions are particularly addressable in light-activated systems. In Rhodobacter sphaeroides reaction centers, charge recombination or back electron transfer from the reduced bacteriopheophytin, HA(-), to the oxidized dimeric bacteriochlorophyll, P(+), may be monitored by both transient absorption spectroscopy and transient fluorescence spectroscopy. Signals measured with both these techniques decay in a similar three-exponential fashion with lifetimes of ∼0.6-0.7, ∼2-4, and ∼10-20 ns, revealing the complex character of this electron transfer reaction. In this study a single kinetic model was developed to connect lifetime and amplitude data from both techniques. The model took into account the possibility that electron transfer from HA(-) to P(+) may occur with transient formation of the state P(+)BA(-). As a result it was possible to model the impact of nanosecond protein relaxation on the free energy levels of both P(+)HA(-) and P(+)BA(-) states relative to that of the singlet excited state of P, P*. Surprisingly, whereas the free energy gap between P* and P(+)HA(-) increased with time in response to protein reorganization, the free energy gap between P* and P(+)BA(-) decreased. This finding may be accounted for by a gradual polarization of the protein environment which stabilizes the state P(+)HA(-) and destabilizes the state P(+)BA(-), favoring productive charge separation over unproductive charge recombination.

Acute delirium, delusion, and depression during IFN-beta-1a therapy for multiple sclerosis: a case report.

Adverse effects of interferon (IFN) treatment are common, and efforts to minimize these reactions are of considerable importance. IFN-beta-1a is an established therapy for patients with relapsing-remitting multiple sclerosis (MS). Its psychiatric side effects are debated and not yet fully established. The authors report here the case of a patient on IFN-beta-1a therapy for MS who developed acute delirium, delusion, and depression that ceased with treatment discontinuation. Although he had a history of recurrent major depressive disorder, his prior psychiatric illness had followed a course that was clinically independent of other signs of MS. This observation points out psychiatric vulnerability of patients taking IFN-beta-1a therapy for MS and suggests that IFN-beta-1a may induce or exacerbate preexisting psychotic symptoms.