The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S] iron–sulfur cluster in an Escherichia coli thioredoxin mutant

Escherichia coli thioredoxin is a small monomeric protein that reduces disulfide bonds in cytoplasmic proteins. Two cysteine residues present in a conserved CGPC motif are essential for this activity. Recently, we identified mutations of this motif that changed thioredoxin into a homodimer bridged by a [2Fe-2S] iron–sulfur cluster. When exported to the periplasm, these thioredoxin mutants could restore disulfide bond formation in strains lacking the entire periplasmic oxidative pathway. Essential for the assembly of the iron–sulfur was an additional cysteine that replaced the proline at position three of the CGPC motif. We solved the crystalline structure at 2.3 Å for one of these variants, TrxA(CACA). The mutant protein crystallized as a dimer in which the iron–sulfur cluster is replaced by two intermolecular disulfide bonds. The catalytic site, which forms the dimer interface, crystallized in two different conformations. In one of them, the replacement of the CGPC motif by CACA has a dramatic effect on the structure and causes the unraveling of an extended α-helix. In both conformations, the second cysteine residue of the CACA motif is surface-exposed, which contrasts with wildtype thioredoxin where the second cysteine of the CXXC motif is buried. This exposure of a pair of vicinal cysteine residues apparently allows thioredoxin to acquire an iron–sulfur cofactor at its active site, and thus a new activity and mechanism of action

Gene expression profiling and heterogeneity of nonspecific orbital inflammation affecting the lacrimal gland

Abstract not available.James T. Rosenbaum, Dongseok Choi, Christina A. Harrington, David J. Wilson, Hans E. Grossniklaus, Cailin H. Sibley, Sherveen S. Salek, John D. Ng, Roger A. Dailey, Eric A. Steele, Brent Hayek, Caroline M. Craven, Deepak P. Edward, Azza M. Y. Maktabi, Hailah Al Hussain, Valerie A. White, Peter J. Dolman, Craig N. Czyz, Jill A. Foster, Gerald J. Harris, Youn-Shen Bee, David T. Tse, Chrisfouad R. Alabiad, Sander R. Dubovy, Michael Kazim, Dinesh Selva, R. Patrick Yeatts, Bobby S. Korn, Don O. Kikkawa, Rona Z. Silkiss, Jennifer A. Sivak-Callcott, Patrick Stauffer, Stephen R. Planc

Conceptualising and measuring defensive marketing orientation (DMO): some inaugural thoughts on assessing marketing's place in 'society's doghouse'

Many have suggested marketing should be at the heart of organisational decision making whilst, coincidentally, lamenting its continued failure to earn strategic sway. Blame is frequently applied to the organisation itself, implying that marketers are unfairly marginalised. For marketing to succeed, however, it must appear both credible and contemporary, yet there is substantive research suggesting, 1) marketing's reputation is far from ideal and, 2) that practitioners remain tethered to traditional means of endeavour, often counter-productive in the context of newer, customer-focused, manifestos. Analysis of both marketing and psychology literatures reveals a lack of tools for determining marketer attitudes toward marketing orientation (MO) or post-MO concerns and, consequently, the commitment of the agent most critical to marketing's aspirations is rarely tested. This paper makes a case for rectifying such discrepancy and, via critical reflection on recent measurement debates, suggests an inaugural perspective on how evaluation might be achieved. An agenda for further research is offered, too