Effects of point mutations in the binding pocket of the mouse major urinary protein MUP20 on ligand affinity and specificity
By Jimena Ricatti, L. Acquasaliente, G. Ribaudo, V. De Filippis, M. Bellini, R. Llovera, S. Barollo, R. Pezzani, G. Zagotto, K. C. Persaud and 1 more. 2019
25 citations recorded by the source corpus.
The mouse Major Urinary Proteins (MUPs) contain a conserved β-barrel structure with a characteristic central hydrophobic pocket that binds a variety of volatile compounds. After release of urine, these molecules are slowly emitted in the environment where they play an important role in chemical communication. MUPs are highly polymorphic and conformationally stable. They may be of interest in the construction of biosensor arrays capable of detection of a broad range of analytes. In this work, 14 critical amino acids in the binding pocket involved in ligand interactions were identified in MUP20 using in silico techniques and 7 MUP20 mutants were synthesised and characterised to produce a set of proteins with diverse ligand binding profiles to structurally different ligands. A single amino acid substitution in the binding pocket can dramatically change the MUPs binding affinity and ligand specificity. These results have great potential for the design of new biosensor and gas-sensor recognition elements.
Subfields: Molecular Biology, Spectroscopy, Computational Biology & Bioinformatics, Computational Chemistry & Drug Discovery
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In Molecular Biology
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In Computational Biology & Bioinformatics
- Alexander Rives
- C. Lawrence Zitnick
- Rob Fergus
- Jerry Ma
- Siddharth Goyal
- Demi Guo
- Myle Ott
- Joshua Meier
Citations in the corpus
- Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences (2019, background): “…function (Romero & Arnold, 2009), inform protein design using a combination of activating mutants (Hu et al., 2018), and make rational substitutions to optimize protein properties such as substrate specificity (Packer et al., 2017), stability (Tan et al., 2014), and binding (Ricatti et al., 2019).”