1,721,036 research outputs found
Birth of a pathway for sulfur metabolism in early amniote evolution
No full textAmong amniotes, reptiles and mammals are differently adapted to terrestrial life. It is well appreciated that terrestrialization required adaptive changes of vertebrate metabolism, particularly in the mode of nitrogen excretion. However, the current paradigm is that metabolic adaptation to life on land did not involve synthesis of enzymatic pathways de novo but repurposing of existing ones. Here, by comparing the inventory of pyridoxal phosphate-dependent enzymes (PLPome) in different amniotes, we identify in silico a pathway for sulfur metabolism present in chick embryos and other reptiles but not in mammals. Cysteine lyase (CL) contains heme and PLP cofactors and converts cysteine and sulfite into cysteic acid and hydrogen sulfide. A specific cysteic acid decarboxylase (CAD) produces taurine while hydrogen sulfide is recycled into cysteine by cystathionine beta-synthase (CBS). This reaction sequence enables the formation of sulfonated amino acids during embryo development in the egg at no cost of reduced sulfur. The pathway originated around 300 million years ago in a proto-reptile by CBS duplication, CL neofunctionalization, and CAD co-option. Our findings indicate that adaptation to terrestrial life involved innovations in metabolic pathways and reveal the molecular mechanisms by which such innovations arose in amniote evolution
A Microbial Metagenome (Leucobacter sp.) in Caenorhabditis Whole Genome Sequences
Full text linkDNA of apparently recent bacterial origin is found in the genomic sequences of Caenorhabditis angaria and Caenorhabditis remanei. Here we present evidence that the DNA belongs to a single species of the genus Leucobacter (high-GC Gram+Actinobacteria). Metagenomic tools enabled the assembly of the contaminating sequences in a draft genome of 3.2 Mb harboring 2,826 genes. This information provides insight into a microbial organism intimately associated with Caenorhabditis as well as a solid basis for the reassignment of 3,373 metazoan entries of the public database to a novel bacterial species ( Leucobacter sp. AEAR). The application of metagenomic techniques can thus prevent annotation errors and reveal unexpected genetic information in data obtained by conventional genomics
The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families
Full text linkAbstract Background - Enzymes that depend on vitamin B6 (and in particular on its metabolically active form, pyridoxal 5'-phosphate, PLP) are of great relevance to biology and medicine, as they catalyze a wide variety of biochemical reactions mainly involving amino acid substrates. Although PLP-dependent enzymes belong to a small number of independent evolutionary lineages, they encompass more than 160 distinct catalytic functions, thus representing a striking example of divergent evolution. The importance and remarkable versatility of these enzymes, as well as the difficulties in their functional classification, create a need for an integrated source of information about them. Description - The B6 database http://bioinformatics.unipr.it/B6db contains documented B6-dependent activities and the relevant protein families, defined as monophyletic groups of sequences possessing the same enzymatic function. One or more families were associated to each of 121 PLP-dependent activities with known sequences. Hidden Markov models (HMMs) were built from family alignments and incorporated in the database. These HMMs can be used for the functional classification of PLP-dependent enzymes in genomic sets of predicted protein sequences. An example of such analyses (a census of human genes coding for PLP-dependent enzymes) is provided here, whereas many more are accessible through the database itself. Conclusion - The B6 database is a curated repository of biochemical and molecular information about an important group of enzymes. This information is logically organized and available for computational analyses, providing a key resource for the identification, classification and comparative analysis of B6-dependent enzymes.</p
[Recent advances in urate metabolism]
No full textNegli ultimi quindici anni la genomica e le altre scienze "omiche" hanno rivoluzionato la nostra conoscenza dei processi biologici a livello molecolare. Un esempio è il metabolismo dell’urato. Prima della pubblicazione del genoma umano, nel 2003, un solo enzima (urato ossidasi) era ritenuto responsabile della degradazione dell’urato (uricolisi), ovvero della sua conversione ad allantoina, un composto molto più solubile e facilmente eliminabile. Oggi sappiamo che questo processo richiede l’azione sequenziale di tre enzimi, che sono stati persi per inattivazione genica in un antenato degli ominoidi. Allo stesso modo, un solo trasportatore dell’urato (URAT1)era noto all’epoca. Attualmente abbiamo evidenze che nelle cellule epiteliali di reni e intestino vi sia un’intera batteria di trasportatori, non ancora del tutto caratterizzati, deputati alla regolazione dell’omeostasi dell’urato. In questa rassegna, riportiamo alcune recenti scoperte sul metabolismo dell’urato, evidenziandone la possibile applicazione allo sviluppo di nuovi farmaci per il trattamento dell’iperuricemia, della sindrome da lisi tumorale e della malattia di Lesch-Nyhan.In the last fifteen years, genomics and other -omics sciences have revolutionized our understanding of biological processes at the molecular level. An illustrative example is urate metabolism. Before the publication of the complete human genome, in 2003 it was believed that a single enzyme (urate oxidase) was responsible for uricolysis that is the conversion of urate into the more soluble allantoin. Now we know with great detail that this process requires the consecutive action of three enzymes that have been lost by gene inactivation in our hominoid ancestor. Similarly, a single urate transporter (URAT1) was known at that time. Now we have evidence that urate homeostasis depends on a complex set of transporters located on the epithelial cells of the kidney and the intestine. In this review article, we give an account of the recent discoveries on urate metabolism and how these discoveries can be applied to the development of novel drugs to treat hyperuricemia, tumor lysis syndrome and the Lesch-Nyhan disease
Selection at the wobble position of codons read by the same tRNA in Saccharomyces cerevisiae
No full textStructural recognition of DNA by poly(ADP-ribose)polymerase-like zinc finger families
No full textPARP-like zinc fingers (zf-PARPs) are protein domains apt to the recognition of multiple DNA secondary structures. They were initially described as the DNA-binding, nick-sensor domains of poly(ADP-ribose)polymerases (PARPs). It now appears that zf-PARPs are evolutionary conserved in the eukaryotic lineage and associated with various enzymes implicated in nucleic acid transactions. In the present study, we discuss the functional and structural data of zf-PARPSs in the light of a comparative analysis of the protein family. Sequence and structural analyses allow the definition of the conserved features of the zf-PARP domain and the identification of five distinct phylogenetic groups. Differences among the groups accumulate on the putative DNA binding surface of the PARP zinc-finger fold. These observations suggest that different zf-PARP types have distinctive recognition properties for DNA secondary structures. A comparison of various functional studies confirms that the different finger types can accomplish a selective recognition of DNA structures
Sequence context effects on oligo(dT) termination signal recognition by Saccharomyces cerevisiae RNA polymerase III
No full textCorrection: Absolute stereochemistry and preferred conformations of urate degradation intermediates from computed and experimental circular dichroism spectra
No full textA novel algorithm for the search of 5S rRNA genes in DNA databases: comparison with other methods and identification of new potential 5S rRNA genes
No full text- …
