A double-deletion method to quantifying incremental binding energies in proteins from experiment. Example of a destabilizing hydrogen bonding pair

The contribution of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory, experiment and simulation. Although hydrogen bonds are major determinants of protein structure and function, their contribution to protein stability is still unclear and widely debated. The best method so far devised to estimate the contribution of side-chain interactions to protein stability is double-mutant-cycle analysis, but the interaction energies so derived are not identical to incremental binding energies (the energies quantifying net contributions of two interacting groups to protein stability). Here we introduce double-deletion analysis of isolated residue pairs as a means to precisely quantify incremental binding. The method is exemplified by studying a surface-exposed hydrogen bond in a model protein (Asp96/Asn128 in apoflavodoxin). Combined substitution of these residues by alanines slightly destabilizes the protein, due to a decrease in hydrophobic surface burial. Subtraction of this effect, however, clearly indicates that the hydrogen-bonded groups in fact destabilize the native conformation. In addition, Molecular Dynamics simulations and classic double-mutant-cycle analysis explain quantitatively that, due to frustration, the hydrogen bond must form in the native structure because, when the two groups get approximated upon folding their binding becomes favorable. We would like to remark two facts: that this is the first time the contribution of a specific hydrogen bond to protein stability has been measured from experiment, and that more hydrogen bonds need to be analyzed in order to draw general conclusions on protein hydrogen bonds energetics. To that end, the double deletion method should be of help.Comment: 41 pages, To appear in Biophysical Journal (in press

PROBLEMES POSES PAR LES VACCINATIONS CONTRE LES VIRUS DU GROUPE DE L'HERPES

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Dysphagie et sténose œsophagienne récidivante associée à une pseudodiverticulose intramurale de l'œsophage. A propos d'un cas clinique

Intramural pseudodiverticulosis of the esophagus is a rare benign disease of the eosphageal wall, with dilation of the submucosal glands, and the predominant symptom is dysphagia. This disorder may be associated with gastroesophageal reflux, motility disorders, candidiasis and alcoholism. Inflammation, resulting in periductal fibrosis and compression of the duct orifices, may be a causative factor. Good and long-lasting therapeutic success can be achieved by bouginage of the stenosis with concomitant treatment of the associated esophageal diseases. Esophageal intramural pseudodiverticulosis is a differential diagnosis in cases of dyspagia and/or esophageal strictures if no other causes are found.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Ileocolonic lesions in patients with seronegative spondylarthropathy

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Hepatic peroxisomes are smaller in primary hyperoxaluria type I (PH I): cytochemistry and morphometry

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Disseminated African histoplasmosis in a white heterosexual male patient with the acquired immune deficiency syndrome

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Endoscopic ultrasonography in achalasia

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hépatite auto-immune associée au syndrome de CREST

We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.SCOPUS: ar.jinfo:eu-repo/semantics/publishe