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MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments

Martins, PM; Navarro, S; Silva, A; Pinto, M; Sárkány, Z; Figueiredo, F; Pereira, PJB; Pinheiro, F; Bednarikova, Z; Burdukiewicz, M; Galzitskaya, OV

Reports on phase separation and amyloid formation for multiple proteins and aggregation-prone peptides are recurrently used to explore the molecular mechanisms associated with several human diseases. The information conveyed by these reports can be used directly in translational investigation, e.g., for the design of better drug screening strategies, or be compiled in databases for benchmarking novel aggregatio...


DisProt: Intrinsic protein disorder annotation in 2020

Hatos, A; Hajdu-Soltész, B; Monzon, AM; Palopoli, N; Álvarez, L; Aykac-Fas, B; Bassot, C; Benítez, GI; Bevilacqua, M; Chasapi, A; Chemes, L; Davey, NE

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interfac...


Molecular fingerprints for a novel enzyme family in actinobacteria with glucosa...

Manso, JA; Nunes-Costa, D; Macedo-Ribeiro, S; Empadinhas, N; Pereira, PJB

Actinobacteria have long been the main source of antibiotics, secondary metabolites with tightly controlled biosynthesis by environmental and physiological factors. Phosphorylation of exogenous glucosamine has been suggested as a mechanism for incorporation of this extracellular material into secondary metabolite biosynthesis, but experimental evidence of specific glucosamine kinases in Actinobacteria is lackin...


Probing the occurrence of soluble oligomers through amyloid aggregation scaling...

Silva, A; Sárkány, Z; Fraga, JS; Taboada, P; Macedo-Ribeiro, S; Martins, PM

Drug discovery frequently relies on the kinetic analysis of physicochemical reactions that are at the origin of the disease state. Amyloid fibril formation has been extensively investigated in relation to prevalent and rare neurodegenerative diseases, but thus far no therapeutic solution has directly arisen from this knowledge. Other aggregation pathways producing smaller, hard-to-detect soluble oligomers are i...


Disclosing the essentiality of ribose-5-phosphate isomerase B in Trypanosomatids

Faria, J; Loureiro, I; Santarém, N; Cecílio, P; Macedo-Ribeiro, S; Tavares, J; Cordeiro-da-Silva, A

Ribose-5-phosphate isomerase (RPI) belongs to the non-oxidative branch of the pentose phosphate pathway, catalysing the inter-conversion of D-ribose-5-phosphate and D-ribulose-5-phosphate. Trypanosomatids encode a type B RPI, whereas humans have a structurally unrelated type A, making RPIB worthy of exploration as a potential drug target. Null mutant generation in Leishmania infantum was only possible when an e...


Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Surviv...

Faria, J; Loureiro, I; Santarém, N; Macedo-Ribeiro, S; Tavares, J; Cordeiro-da-Silva, A

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in human...


Ataxin-3 phosphorylation decreases neuronal defects in spinocerebellar ataxia t...

Matos, C; Nóbrega, C; Louros, S; Almeida, B; Ferreiro, E; Valero, J; Almeida, L; Macedo-Ribeiro, S; Carvalho, A

Different neurodegenerative diseases are caused by aberrant elongation of repeated glutamine sequences normally found in particular human proteins. Although the proteins involved are ubiquitously distributed in human tissues, toxicity targets only defined neuronal populations. Changes caused by an expanded polyglutamine protein are possibly influenced by endogenous cellular mechanisms, which may be harnessed to...


Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodst...

Loureiro, I; Faria, J; Clayton, C; Macedo-Ribeiro, S; Santarém, N; Roy, N; Cordeiro-da-Siva, A; Tavares, J

Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose...


The unique regulation of iron-sulfur cluster biogenesis in a Gram-positive bact...

Santos, JA; Alonso-García, N; Macedo-Ribeiro, S; Pereira, PJ

Iron-sulfur clusters function as cofactors of a wide range of proteins, with diverse molecular roles in both prokaryotic and eukaryotic cells. Dedicated machineries assemble the clusters and deliver them to the final acceptor molecules in a tightly regulated process. In the prototypical Gram-negative bacterium Escherichia coli, the two existing iron-sulfur cluster assembly systems, iron-sulfur cluster (ISC) and...


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