The monotopic, endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) undergo variable proteolytic turnover. CYP3A4, the dominant human liver drug-metabolizing enzyme, is degraded via a ubiquitin (Ub)-dependent 26S proteasomal pathway after heterologous expression in Saccharomyces cerevisiae. This turnover involves the Ub-conjugating enzyme Ubc7p and the 19S proteasomal subunit Hrd2p but ...

Overlapping open reading frames (ORFs) in viral genomes undergo co-evolution; however, how individual amino acids coded by overlapping ORFs are structurally, functionally, and co-evolutionarily constrained remains difficult to address by conventional homologous sequence alignment approaches. We report here a new experimental and computational evolution-based methodology to address this question...

INTRODUCTION The presence of Angiotensin (1-7) (Ang 1-7) and ACE 2 in the ventricle of cardiomyopathic hamsters as well as the influence of Ang (1-7) on membrane potential, impulse propagation and cardiac excitability were investigated. METHODS Histology and immunochemistry were used to demonstrate the presence of Ang (1-7) and ACE 2 in the ventricle of cardiomyopathic hamsters. Measurements ...

KOIKE e t al. reported that a cationic acylpeptide antibiotic, colistin (polymyxin E) caused the formation of blebs on the outer layer of the Gram-negative bacterial cell envelope". They have also reported that colistin affects the cytoplasmic membrane, leads to leakage of cytoplasmic 260 nm-absorbing materials and has specific bursting-activity on spheroplasts of Gram-negative bacteria'). On t...

Lung cancer is one of the most frequent types of cancer in humans and a leading cause of death worldwide. The high mortality rates are correlated with late diagnosis, which leads to high rates of metastasis found in patients. Thus, despite all the improvement in therapeutic approaches, the development of new drugs that control cancer cell migration and metastasis are required. The heptapeptide ...

UNLABELLED Escherichia coli microcin C (McC) consists of a ribosomally synthesized heptapeptide attached to a modified adenosine. McC is actively taken up by sensitive Escherichia coli strains through the YejABEF transporter. Inside the cell, McC is processed by aminopeptidases, which release nonhydrolyzable aminoacyl adenylate, an inhibitor of aspartyl-tRNA synthetase. McC is synthesized by th...

Models of early protein evolution posit the existence of short peptides that bound metals and ions and served as transporters, membranes or catalysts. The Cys-X-X-Cys-X-X-Cys heptapeptide located within bacterial ferredoxins, enclosing an Fe₄S₄ metal center, is an attractive candidate for such an early peptide. Ferredoxins are ancient proteins and the simple α+β fold is found alone or as a doma...

Chloroeremomycin, a vancomycin family glycopeptide antibiotic has three sugars, one D-glucose and two L-4-epi-vancosamines, attached to the crosslinked heptapeptide backbone by three glycosyltransferases, GtfA, -B, and -C. Prior efforts have revealed that GtfB and -C in tandem build an epivancosaminyl-1,2-glucosyldisaccharide chain on residue 4 of the aglycone; however, the characterization of ...

The flavoenzyme D-amino acid oxidase (Eo) is rapidly chlorinated by N-chloro-D-leucine (Rudie, N.G., Porter, D.J.T., and Bright, H.J. (1980) J. Biol. Chem. 255, 498-508). We have carried out chymotryptic digestion of E0-36Cl2 and find that all of the radiolabel is located in a heptapeptide having [3.5-36Cl2]chlorotyrosine as the COOH-terminal residue. This heptapeptide, having the sequence -Asp...