Combined chemical shift changes and amino acid specific chemical shift mapping of protein–protein interactions

Abstract

Protein-protein interactions are often studied by chemical shift mapping using solution NMR spectroscopy. When heteronuclear data are available the interaction interface is usually predicted by combining the chemical shift changes of different nuclei to a single quantity, the combined chemical shift perturbation Deltadelta comb In this paper different procedures (published and non-published) to calculate Deltadelta comb are examined that include a variety of different functional forms and weighting factors for each nucleus. The predictive power of all shift mapping methods depends on the magnitude of the overlap of the chemical shift distributions of interacting and non-interacting residues and the cut-off criterion used. In general, the quality of the prediction on the basis of chemical shift changes alone is rather unsatisfactory but the combination of chemical shift changes on the basis of the Hamming or the Euclidian distance can improve the result. The corrected standard deviation to zero of the combined chemical shift changes can provide a reasonable cut-off criterion. As we show combined chemical shifts can also be applied for a more reliable quantitative evaluation of titration data.

The Tyrosine Kinase c-Src Specifically Binds to the Active Integrin αIIbβ3 to Initiate Outside-in Signaling in Platelets

“…Chemical shift assignments for the SH3 domain were referenced to the assignments in almost identical conditions (100 mM phosphate pH 6.0, 100 mM NaCl and 25°C, BMRB ID 3433) (25). Thresholds for chemical shift changes indicative of specific protein-protein interactions were calculated using the method of Schumann et al (26).…”

Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid

“…The spectra were zero-filled twice and apodised with a squared sine bell function shifted by p/2 in both dimensions, using linear prediction of the data in the incremented dimension. The combined chemical shift changes, which include information of both involved nuclei and are more convenient to analyze 1 H/ 13 C HSQC data, were used [49]. The combined chemical shift changes Dd 1 H/ 13 C were calculated from 1 H to 13 It is expressed as: w ¼ jg 13C j/jg 1H j where g 13C and g 1H are magnetogyric ratios of 13 C nucleus and the proton, respectively [49].…”

The interaction of ammonia and xenon with the imidazole glycerol phosphate synthase from Thermotoga maritima as detected by NMR spectroscopy

“…The observed chemical shift changes were analyzed by calculating the so-called total xenon-induced chemical shift (D) from the xenon-induced 1 H and 15 N chemical shifts as suggested by Gröger et al 15 The result of this analysis is shown in Figure 6. Note that the calculation of the combined chemical shifts, according to Schumann et al, 19 led to very similar Table I. These residues are considered to be strongly influenced by xenon binding.…”