25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Methionine renaissance: computing methyl NMR assignments from X-ray structures

27 Aug 2019, 12:30
Lecture Hall B (Henry Ford Building)

Lecture Hall B

Henry Ford Building

Talk Computation Computation


Prof. Miquel Pons (University of Barcelona)


Methyl groups are privileged probes for the NMR study of large proteins. Methionine is the least abundant of the methyl-containing amino acids but is often directly connected to functionally important sites. While isotopic labeling with 13CH3-methionine is straightforward, assignment of the resulting spectra is challenging and often requires site-specific mutation of each of the methionines in the protein. Standard methods based on through-bond correlation to assigned backbone resonances or by matching observed and predicted inter-methyl NOEs on the basis of known X-ray structures are not applicable to exclusively methyl-methionine labeled proteins.
In this communication we will show that methionine methyl groups chemical shifts can be predicted from X-ray structures based on fast quantum chemical calculations on simplified models. The use of quantum chemical calculations outperforms the statistics-based predictions in the case of the scarce and flexible methionine residues. The calculated chemical shifts successfully predict the correct assignment or, at least, helps to define the minimal number of mutations needed to complete it.
Methyl methionine NMR has been used to functionally characterize the catalytic domains of calcineurin (345 residues, 7 methionines) and Src (253 residues, 10 methionines).
In the case of calcineurin, methionine methyl signals probe the binding of peptides and the conservation of a cis peptide bond in the mutant in which the native P84 was replaced by alanine [1].

Acknowledgements. Supported in part by grant BIO2016-78006R and by access to the R-LRB, the Spanish NMR facility network.


  1. Teixeira, J.M.C., Guasch, A., Biçer, A., Aranguren-Ibáñez, A., Chasmniam, S., Paniagua, J.C., Pérez-Riba, M., Fita, I. , Pons, M. Cis-trans proline isomers in the catalytic domain of calcineurin. FEBS J. 286, 1230-1239 (2019)

Primary authors

Dr Saeed Chasmniam (University of Barcelona (Spain); Sharif University (Iran)) Prof. Juan Carlos Paniagua (University of Barcelona) Dr Joao M.C. Teixeira (University of Barcelona) Mr Héctor Fuentes (University of Barcelona) Prof. Miquel Pons (University of Barcelona)

Presentation Materials

There are no materials yet.