N-terminal pyroglutamate (pGlu) formation from its glutaminyl (or glutamyl) precursor is required in the maturation of numerous bioactive peptides. The aberrant formation of pGlu may be related to several pathological processes, such as osteoporosis and amyloidotic diseases. This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC). To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors. The structure reveals an ␣͞␤ scaffold akin to that of two-zinc exopeptidases but with several insertions and deletions, particularly in the active-site region. The relatively closed active site displays alternate conformations due to the different indole orientations of Trp-207, resulting in two substrate (glutamine t-butyl ester)-binding modes. The single zinc ion in the active site is coordinated to three conserved residues and one water molecule, which is replaced by an imidazole nitrogen upon binding of the inhibitors. Together with structural and kinetic analyses of several active-site-mutant enzymes, a catalysis mechanism of the formation of protein N-terminal pGlu is proposed. Our results provide a structural basis for the rational design of inhibitors against QC-associated disorders.crystallography ͉ intramolecular cyclization ͉ posttranslational modification ͉ Alzheimer's disease ͉ aminopeptidase N -terminal pyroglutamate (pGlu) formation from its glutaminyl precursor is an important posttranslational or cotranslational event in the processing of numerous bioactive neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. These regulatory peptides require the N-terminal pGlu to develop the proper conformation for binding to their receptors and͞or to protect the N termini of the peptides from exopeptidase degradation (1, 2). Previously, this Nterminal cyclization reaction was thought to proceed spontaneously, until the glutaminyl cyclases (QCs) were identified as catalysts that are responsible for this posttranslational modification (3, 4).QCs (EC 2.3.2.5) are acyltransferases that have been identified in both animal and plant sources (3-5). They are abundant in mammalian neuroendocrine tissues, such as hypothalamus and pituitary (4, 6), and are highly conserved from yeast to human. Animal QCs were shown to have distinct structure and protein stability from plant QCs despite their similar molecular masses [i.e., 33-40 kDa (5, 7)]. No bacterial QCs have been reported thus far; however, the mammalian QCs were predicted to exhibit remarkable homology to the bacterial double-zinc aminopeptidases (8, 9).In humans, several genetic diseases, such as osteoporosis, a multifactorial hormonal disease that is characterized by reduced bone mass and microarchitectural deterioration of bone tissue (10), appear to result from mutations of the QC gene. The gene encoding QC (QPCT) lies on chromosome 2p22.3. ...

The effect of gelatinization and retrogradation of the popular binder, guar gum, on the dispersion of electrode constituents and the cell performance of the lithium-sulfur battery is studied. When guar gum is added in a gelatinized state, the fabricated electrode slurry adopts a gel-like structure, leading to the poor dispersion of constituents and poor electrochemistry of constructed cells. With the addition of retrograded guar gum, the prepared slurry is not gelled, and the dispersion of constituents and the cell performance are both greatly improved.

The use of poly(4‐styrene sulfonic acid) (PSSA) to effectively disperse graphene in an aqueous sulfur (S) cathode slurry is proposed, and the cell performance of the resulting Li−S battery is investigated and compared to that of the battery prepared by adding as‐received graphene. The addition of PSSA improves not only the dispersion of the as‐received graphene, but also the homogeneity of the constituents in the S cathode slurry; accordingly, better electronic and ionic conductivities are obtained. The electrical impedance of the cell constructed using the S cathode with the as‐received graphene is greatly reduced from 142.0 to 14.6 Ω when PSSA is added during the preparation of the cathode. Moreover, the addition of the PSSA‐dispersed graphene to the S cathode significantly improves the capacity, cycle life, and coulombic efficiency during the charge‐discharge process, since PSSA increases the contact between the dispersed graphene and the insulated S powder.

The front cover artwork is provided by Prof. Chia‐Chen Li's group from the Department of Materials and Mineral Resources Engineering, National Taipei University of Technology (Taiwan). The cover picture shows an effective dispersant, poly(4‐styrene sulfonic acid) (PSSA), for graphene. The addition of the PSSA‐dispersed graphene to a sulfur cathode improves the cell performance of Li–S batteries. Read the full text of the Communication at https://doi.org/10.1002/celc.201801251.

The Front Cover shows an effective additive, poly(4‐styrene sulfonic acid), for the dispersion of graphene. The addition of poly(4‐styrene sulfonic acid)‐dispersed graphene to a sulfur cathode improves the capacity, cycle life, and coulombic efficiency of the constructed Li–S cell, as the contact between the dispersed graphene and the insulated sulfur powder is increased. More information can be found in the Communication by W.‐J. Cheng et al. on page 3835 in Issue 24, 2018 (DOI: 10.1002/celc.201801251).