Protein Conformation

Publication Title: 
FEBS letters

Strains of Caenorhabditis elegans mutant for clk-1 exhibit a 20-40% increase in mean lifespan. clk-1 encodes a mitochondrial protein thought to be either an enzyme or regulatory molecule acting within the ubiquinone biosynthesis pathway. Here CLK-1 is shown to be related to the ubiquinol oxidase, alternative oxidase, and belong to the functionally diverse di-iron-carboxylate protein family which includes bacterioferritin and methane mono-oxygenase.

Author(s): 
Rea, S.
Publication Title: 
Handbook of Experimental Pharmacology

Members of the sirtuin family including the founding protein Sir2 in Saccharomyces cerevisiae have been linked to lifespan extension in simple organisms. This finding prompted evaluation of the role of Sir2 orthologues in many aging-associated conditions including neurodegeneration, type II diabetes and cancer.

Author(s): 
Mahajan, Sumit S.
Leko, Vid
Simon, Julian A.
Bedalov, Antonio
Publication Title: 
Neuromolecular Medicine

A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.

Author(s): 
Zetterstrˆm, Per
Graffmo, Karin S.
Andersen, Peter M.
Br‰nnstrˆm, Thomas
Marklund, Stefan L.
Publication Title: 
Molecular Aspects of Medicine

The SLC16 gene family has fourteen members. Four (SLC16A1, SLC16A3, SLC16A7, and SLC16A8) encode monocarboxylate transporters (MCT1, MCT4, MCT2, and MCT3, respectively) catalysing the proton-linked transport of monocarboxylates such as l-lactate, pyruvate and ketone bodies across the plasma membrane. SLC16A2 encodes a high affinity thyroid hormone transporter (MCT8) and SLC16A10 an aromatic amino acid transporter (TAT1). The substrates and roles of the remaining eight members are unknown.

Author(s): 
Halestrap, Andrew P.
Publication Title: 
PloS One

Aging in the world population has increased every year. Superoxide dismutase 2 (Mn-SOD or SOD2) protects against oxidative stress, a main factor influencing cellular longevity. Polymorphisms in SOD2 have been associated with the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, as well as psychiatric disorders, such as schizophrenia, depression and bipolar disorder.

Author(s): 
de Carvalho, Mariana Dias Castela
De Mesquita, Joelma Freire
Publication Title: 
Neuromolecular Medicine

Emerging lines of evidence suggest a relationship between amyotrophic lateral sclerosis (ALS) and protein sumoylation. Multiple studies have demonstrated that several of the proteins involved in the pathogenesis of ALS, including superoxide dismutase 1, fused in liposarcoma, and TAR DNA-binding protein 43 (TDP-43), are substrates for sumoylation.

Author(s): 
Foran, Emily
Rosenblum, Lauren
Bogush, Alexey I.
Trotti, Davide
Publication Title: 
Genes & Development

The ribonucleoprotein (RNP) enzyme telomerase from Saccharomyces cerevisiae adds telomeric DNA to chromosomal ends in short increments both in vivo and in vitro. Whether or not telomerase functions as a multimer has not been addressed previously. Here we show, first, that following polymerization, the telomerase RNP remains stably bound to its telomeric oligonucleotide reaction product. We then exploit this finding and a previously reported mutant telomerase RNA to demonstrate that, unexpectedly, the S.

Author(s): 
Prescott, J.
Blackburn, E. H.
Publication Title: 
Biophysical Journal

In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe) and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate (NMDA) receptor. Using x-ray crystallography, we examined the binding characteristics of these two gases on two soluble proteins as structural models: urate oxidase, which is a prototype of a variety of intracellular globular proteins, and annexin V, which has structural and functional characteristics that allow it to be considered as a prototype for the NMDA receptor. The structure of these proteins complexed with Xe and N(2)O were determined.

Author(s): 
Colloc'h, Nathalie
Sopkova-de Oliveira Santos, Jana
Retailleau, Pascal
Vivarès, Denis
Bonneté, Françoise
Langlois d'Estainto, Béatrice
Gallois, Bernard
Brisson, Alain
Risso, Jean-Jacques
Lemaire, Marc
Prangé, Thierry
Abraini, Jacques H.
Publication Title: 
FEBS letters

Artemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua. CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha-4,11-diene to produce artemisinic acid. In this study, we isolated putative CYP71AV1 orthologs in different species of Artemisia.

Author(s): 
Komori, Aya
Suzuki, Munenori
Seki, Hikaru
Nishizawa, Tomoko
Meyer, Jacobus Johannes Marion
Shimizu, Hideaki
Yokoyama, Shigeyuki
Muranaka, Toshiya
Publication Title: 
Malaria Journal

BACKGROUND: The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. Because artemisinin derivatives are now used in the most effective anti-malarial therapy, resistance to artemisinin would be catastrophic. Indeed, studies suggest that artemisinin resistance has already appeared in natural infections. Understanding the mechanisms of resistance would help to prolong the effective lifetime of these drugs. Genetic markers of resistance are therefore required urgently.

Author(s): 
Henriques, Gisela
Martinelli, Axel
Rodrigues, Louise
Modrzynska, Katarzyna
Fawcett, Richard
Houston, Douglas R.
Borges, Sofia T.
D'Alessandro, Umberto
Tinto, Halidou
Karema, Corine
Hunt, Paul
Cravo, Pedro

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