The synthesis and characterization of water-soluble random copolymers containing L-glutamic acid with N5-(4-hydroxybutyl)-L-glutamine and the thermally induced helix-coil transitions of these copolymers in water and in 0.1 N KCl are described. The incorporation of L-glutamic acid was found to increase the helix content of the polymer at low pH and to decrease it at high pH even though the presence of 0.1 N KCl effectively eliminated the difference between the electrostatic free energies of the helix and the coil. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-glutamic acid) in water and in 0.1 N KCl were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The synthesis of N-acetyl-N'-methylglutamic acid amide and its titration, as well as that of the copolymers and poly(L-glutamic acid), in 0.1 N KCl are described.

In Mycobacterium tuberculosis (Mtb), the Clp protease degradation pathway, mediated by the modular ClpCP and ClpXP protease complexes, is essential for growth and presents an attractive drug target. Employing a bacterial adenylate cyclase two‐hybrid (BACTH) screening approach that we adapted to screen the proteome of an Mtb ORF library, we identify protein interaction partners of the ClpC1 chaperone on a genome‐wide level. Our results demonstrate that bipartite type II toxin–antitoxin (TA) systems represent a major substrate class. Out of the 67 type II TA systems known in Mtb, 25 appear as ClpC1 interaction partners in the BACTH screen, including members of the VapBC, MazEF, and ParDE families, as well as a RelBE member that was identified biochemically. We show that antitoxins of the Vap and Rel families are degraded by ClpCP in vitro. We also demonstrate that ClpCP is responsible for mediating the N‐end rule pathway, since the adaptor protein ClpS supports ClpC‐dependent degradation of an N‐end rule model substrate in vitro.

Highlights d Cyclomarin A (CymA) activates the AAA+ protease ClpC/ClpP d CymA overrides ClpC/ClpP activity control by mimicking adapter protein binding d CymA-activated ClpC/ClpP causes cell death by uncontrolled protein degradation

Diagnosis and follow-up of renal disease diagnosed in pregnancy is important as progressive disease occurs in this group. Routine antenatal screening provides a useful diagnostic opportunity to detect asymptomatic renal disease. In a selected sub-group, renal biopsy during pregnancy can be helpful in initiation of correct treatment and allowing progression of pregnancy to fetal viability.

The synthesis and characterization of water-soluble "random" copolymers containing L-valine with either AMS-hydroxypropyll-L-glutamine or iV5-(4-hydroxybutyl)-L-glutamine are described, and the thermally induced helix-coil transitions of these copolymers in water have been studied. The incorporation of L-valine was found to decrease the helix content of the polymer at low temperatures and increase it at high temperatures. The Zimm-Bragg parameters and s for the helix-coil transition in poly(L-valine) in water were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. This is a continuation of previous papers3"9• of this series in which random copolymers are used [in the "host-guest" technique with either A^-CS-hydroxypropylJ-L-glutamine (HPG) or iV5-(4-hydroxybutyl)-L-glutamine (HBG) as the host residue] for the evaluation of the helix-coil stability constants of the naturally occurring amino acids in water. The technique is applied here to obtain the Zimm-Bragg parameters10 and s for L-valine.It has previously been shown qualitatively that (in organic solvents) L-valine reduces the stability of a-helices in a random11 copolymer, and either increases or decreases the stability of a helices (depending on the amino acid sequence) in regular-sequence12 copolymers; in block copolymers,13 poly(L-valine) assumes a ß structure in water but an -helical one in methanol. The results described here confirm the earlier qualitative work that poly(L-valine) is nonhelical in water (at least at low temperature), and also provide a quantitative description (in terms of and s) of the conformational preference of lvaline in water over the temperature range of 0-70°.The synthesis of water-soluble random copolymers of lvaline with either HPG or HBG is described in section I, and the experimental characterization of these copolymers and their melting behavior in water are presented in section II. Finally, in section III, the data are analyzed by means of an appropriate form of the theory3 to determine the helix-coil stability parameters of L-valine in water.