The functional importance of co-evolving residues in proteins

Computational approaches for detecting co-evolution in proteins allow for the identification of protein–protein interaction networks in different organisms and the assignment of function to under-explored proteins. The detection of co-variation of amino acids within or between proteins, moreover, allows for the discovery of residue–residue contacts and highlights functional residues that can affect the binding affinity, catalytic activity, or substrate specificity of a protein. To explore the functional impact of co-evolutionary changes in proteins, a combined experimental and computational approach must be recruited. Here, we review recent studies that apply computational and experimental tools to obtain novel insight into the structure, function, and evolution of proteins. Specifically, we describe the application of co-evolutionary analysis for predicting high-resolution three-dimensional structures of proteins. In addition, we describe computational approaches followed by experimental analysis for identifying specificity-determining residues in proteins. Finally, we discuss studies addressing the importance of such residues in terms of the functional divergence of proteins, allowing proteins to evolve new functions while avoiding crosstalk with existing cellular pathways or forming reproductive barriers and hence promoting speciation.     

Threo-3,4-Dihydroxyphenylserine,a poor source of noradrenaline in the rat

Résumé Chez le rat, les injections dedl-thréo-3,4-dihydroxyphénylsérine, un précurseur pharmacologique synthétique de la noradrénaline, provoquent une conversion de moins de 1% au 4-hydroxy-3-méthoxyphényl-glycol, le métabolite urinaire majeur de la noradrénaline dans cette espèce. Un nouveau cheminement qui entraîne une coupure latérale de la chaîne prit environ 10% de la dose et un autre 10% fût excrété comme un amino-acideO-méthylé; le sort de quelque 80% est inconnu.     

The effect of phenazine methosulfate on the activity of dehydrogenases as studied by starch gel electrophoresis

Résumé L'effet de la phenazine methosulfate (PMS) sur l'activité de plusieurs enzymes oxydatifs a été étudié. En tant que transporteur d'électron, la PMS a un rôle important sur la coloration des isoenzymes séparés par électrophorèse en gel d'amidon. En ce qui concerne la déshydrogénase lactique, un excès de PMS provoque une coloration diffuse, alors que dans le cas de la déshydrogénase succinique on observe l'apparition de «bandes négatives» qui n'ont pas encore été décrites.

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This work was supported by grants Nos. HEO4553, HeO45691, and FRO0165 of the National Institute of Health. The technical assistance of Mr. R.Hernandez is gratefully acknowledged.     

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Summary Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were, higher than in S-rats (p<0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p<0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.