The binding cavity of mouse major urinary protein is optimised for a variety of ligand binding modes

¹⁵N and ¹HN chemical shift data and ¹⁵N relaxation studies have been used to characterise the binding of N-phenyl-naphthylamine (NPN) to mouse major urinary protein (MUP). NPN binds in the β-barrel cavity of MUP, hydrogen bonding to Tyr120 and making extensive non-bonded contacts with hydrophobic side chains. In contrast to the natural pheromone 2-sec-butyl-4,5-dihydrothiazole, NPN binding gives no change to the overall mobility of the protein backbone of MUP. Comparison with 11 different ligands that bind to MUP shows a range of binding modes involving 16 different residues in the β-barrel cavity. These finding justify why MUP is able to adapt to allow for many successful binding partners.