effects of missense r84q mutation on human pyrroline-5-carboxylate synthase enzyme properties, an in-silico analysis
نویسندگان
چکیده
mammalian ∆-(1)-pyrroline-5-carboxylate synthase (p5cs) enzyme catalyzes the coupled phosphorylation and reduction-conversion of glutamate to ∆-(1)-pyrroline-5-carboxylate (p5c), a critical step in the proline, ornithine, citrulline and arginine biosynthesis. in plants and mammals, p5cs consists of two separate enzymatic domains: n-terminal γ-glutamyl kinase (γ-gk) and c-terminal γ-glutamyl phosphate reductase (γ–gpr). hyperammonemia has been reported as a new inborn disorder, with a range of clinical symptoms which is associated with a reduced synthesis of proline, ornithine, citruline and arginine. a missense mutation, r84q, which alters the conserved residue in γ-gk domain, is responsible for this disorder. in this study using in-silico approaches as a new bioinformatics method, sequence analysis was performed and the tertiary structure of γ-gk domain of human p5cs, which includes the r84q missense mutation, was predicted and the mutation effects on structural and functional features of p5cs enzyme were analyzed. our analysis showed that this substitution has an affect on the molecular surface accessibility and total energy of the modeled structure. we conclude that this mutation results in a reduced activity of p5cs enzyme and an impaired synthesis of these amino acids.
منابع مشابه
Pyrroline-5-carboxylate synthase activity in mammalian cells.
Although glutamic acid is known to be a precursor for proline biosynthesis, the enzymatic conversion of glutamic acid to pyrroline-5-carboxylic acid, the immediate precursor of proline, has not been demonstrated in cell-free systems. By providing appropriate concentrations of ATP and NADPH and blocking further metabolism of pyrroline-5-carboxylic acid, we have developed a method for measuring t...
متن کاملCrystal structure of human pyrroline-5-carboxylate reductase.
Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Angstroms resolution structure...
متن کاملResolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1.
Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knock-out suppresses tumorigenic growth...
متن کاملPurification, characterization, and crystallization of human pyrroline-5-carboxylate reductase.
Pyrroline-5-carboxylate reductase (P5CR) catalyzes the reduction of Delta1-pyrroline-5-carboxylate (P5C) to proline with concomitant oxidation of NAD(P)H to NAD(P)(+). The enzymatic cycle between P5C and proline is very important in many physiological and pathological processes. Human P5CR was over-expressed in Escherichia coli and purified to homogeneity by chromatography. Enzymatic assays of ...
متن کاملPurification to homogeneity of pyrroline-5-carboxylate reductase of barley.
An enzyme has been purified to homogeneity from barley seedlings which has ;proline dehydrogenase' and the pyrroline-5-carboxylic acid reductase activities. The purification achieved is 39,000-fold as calculated from the proline dehydrogenase activity. The subunit molecular weight of the protein is 30 kilodaltons. The native enzyme has molecular weights up to 480 kilodaltons, depending on the b...
متن کاملPyrroline-5-carboxylate reductase of Neurospora crassa; partial purification and some properties.
Previous studies (1, 2) with mutant and wild type strains of Neurospora crassa have pointed to glutamic y-semialdehyde and its spontaneously cyclized form, Al-pyrroline-5-carboxylate, as intermediates in the biosynthesis of proline. These studies, based largely on experiments in vivo, have recently been substantiated through work in vitro with extracted enzymes (3, 4). ‘The terminal step in pro...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
applied biotechnology reportsجلد ۱، شماره ۱، صفحات ۰-۰
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023