A supra-massive magnetar central engine for short GRB 130603B

We show that the peculiar early optical and in particular X-ray afterglow emission of the short duration burst GRB 130603B can be explained by continuous energy injection into the blastwave from a supra-massive magnetar central engine. The observed energetics and temporal/spectral properties of the late infrared bump (i.e., the "kilonova") are also found consistent with emission from the ejecta launched during an NS-NS merger and powered by a magnetar central engine. The isotropic-equivalent kinetic energies of both the GRB blastwave and the kilonova are about $E_{\rm k}\sim 10^{51}$ erg, consistent with being powered by a near-isotropic magnetar wind. However, this relatively small value demands that most of the initial rotational energy of the magnetar $(\sim {\rm a~ few \times 10^{52}~ erg})$ is carried away by gravitational wave radiation. Our results suggest that (i) the progenitor of GRB 130603B would be a NS-NS binary system, whose merger product would be a supra-massive neutron star that lasted for about $\sim 1000$ seconds; (ii) the equation-of-state of nuclear matter would be stiff enough to allow survival of a long-lived supra-massive neutron star, so that it is promising to detect bright electromagnetic counterparts of gravitational wave triggers without short GRB associations in the upcoming Advanced LIGO/Virgo era.Comment: Five pages including 1 Figure, to appear in ApJ

7-[4-(5,7-Dimethyl-1,8-naphthyridin-2-yl­oxy)phen­oxy]-2,4-dimethyl-1,8-naphthyridine methanol disolvate

The title compound, C26H22N4O2·2CH3OH, was synthesized and characterized by 1H NMR spectroscopy and X-ray structure analysis. There is one half-mol­ecule in the asymmetric unit with a centre of symmetry located at the centre of the benzene ring. The two bridged naphthyridine ring systems are in an anti­parallel orientation. In the crystal structure, O—H⋯N, C—H⋯O and C—H⋯N inter­actions define the packing

5-Methyl-1,2,3,3a-tetra­hydro­benzo[e]pyrrolo­[2,1-b][1,3]oxazepin-10(5H)-one

The asymmetric unit of the title compound, C13H15NO2, the main product of a photoreaction, contains two crystallographically independent mol­ecules. In both mol­ecules, the conformation of the seven-membered ring is twist sofa and that of the five-membered rings is envelope. In the crystal, mol­ecules are linked by weak inter­molecular C—H⋯O hydrogen bonds

Conserved Loop Cysteines of Vitamin K Epoxide Reductase Complex Subunit 1-like 1 (VKORC1L1) Are Involved in Its Active Site Regeneration

Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions

Mycobacterium tuberculosis Vitamin K Epoxide Reductase Homologue Supports Vitamin K–Dependent Carboxylation in Mammalian Cells

Aims: Vitamin K epoxide reductase complex, subunit 1 (VKORC1) is a critical participant in the production of active forms of reduced vitamin K and is required for modification of vitamin K–dependent proteins. Homologues of VKORC1 (VKORH) exist throughout evolution, but in bacteria they appear to function in oxidative protein folding as well as quinone reduction. In the current study we explore two questions: Do VKORHs function in the mammalian vitamin K cycle? Is the pair of loop cysteines—C43 and C51 in human VKORC1—conserved in all VKORC1s, essential for the activity of vitamin K epoxide reduction? Results: We used our recently developed cell-based assay to compare the function of VKORHs to that of human VKORC1 in mammalian cells. We identified for the first time a VKORH (from Mycobacterium tuberculosis [Mt-VKORH]) that can function in the mammalian vitamin K cycle with vitamin K epoxide or vitamin K as substrate. Consistent with our previous in vitro results, the loop cysteines of human VKORC1 are not essential for its activity in vivo. Moreover, the corresponding loop cysteines of Mt-VKORH (C57 and C65), which are essential for its activity in disulfide bond formation during protein folding in Escherichia coli, are not required in the mammalian vitamin K cycle. Innovation and Conclusions: Our results indicate that VKORC1 in eukaryotes and Mt-VKORH in bacteria, that is, in their respective native environments, employ apparently different mechanisms for electron transfer. However, when Mt-VKORH is in the mammalian cell system, it employs a mechanism similar to that of VKORC1. Antioxid. Redox Signal. 16, 329–338