Pgp (P-glycoprotein) is a prototype ABC (ATP-binding-cassette) transporter involved in multidrug resistance of cancer. We used directed evolution to replace six cytoplasmic Cys (cysteine) residues in Pgp with all 20 standard amino acids and selected for active mutants. From a pool of 75000 transformants for each block of three Cys, we identified multiple mutants that preserved drug resistance a...

reaction of glycin with malononitrile afforded respective pyrrole. pyrrole is one of the heterocyclic compounds with very important biological activities. heterocycles are extremely important because of their wide range of applications that goes from their use as pharmaceuticals and agrochemicals to dyestuffs and additives. in this view, it was proposed to synthesize pyrrole-3-carbonitrile deri...

OBJECTIVE Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage attributed to oxidative stress. We tested the hypothesis that diminished GSH in adult patients with uncontrolled type 2 diabetes is attributed to decreased synthesis and measured the effect of dietary supplementation with its precursors cysteine and glycine...

BACKGROUND Aging is associated with oxidative stress, but underlying mechanisms remain poorly understood. OBJECTIVE We tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. DESIGN Eight elderly and 8 youn...

Glycine-rich proteins (GRPs) derived from plants compose a family of proteins and peptides that share a glycine repeat domain and they can perform diverse functions. Two structural conformations have been proposed for GRPs: glycine loops arranged as a Velcro and an anti-parallel β-sheet with several β-strands. The antimicrobial peptide Pg-AMP1 is the only plant GRP with antibacterial activity r...

Vitamin B12 (cobalamin, Cbl) deficiency can cause metabolic, hematological, and neurological abnormalities. Adequate levels of succinyl-coenzyme A (CoA) cannot be synthesized from methylmalonyl-CoA because of the decreased activity of the methylmalonyl-CoA mutase enzyme that uses Cbl as the cofactor. Succinyl-CoA synthesis deficiency leads to decreased heme synthesis and gluconeogenesis. The re...