Engineering lanmodulin's selectivity for actinides over lanthanides by controlling solvent coordination and...

Area of Science:

• Biochemistry and biophysics
• Coordination chemistry
• Radiochemistry

Background:

• Developing selective chelators for lanthanides and actinides is critical for rare earths mining, nuclear waste management, and medicine.
• Lanmodulin (LanM) is a highly selective protein chelator for f-elements, but its mechanism of action is not fully understood.
• Achieving selectivity between actinides and lanthanides is a significant challenge in chelator design.

Purpose of the Study:

• To investigate the role of the aspartate residue at the 9th position in LanM's metal-binding sites.
• To understand how LanM achieves high affinity and selectivity for f-elements.
• To explore strategies for improving LanM's actinide/lanthanide selectivity.

Main Methods:

• Characterization of five LanM variants with substitutions at the 9th aspartate position (asparagine, histidine, alanine, methionine, selenomethionine).
• Spectroscopic measurements using lanthanides (Nd3+, Eu3+) and actinides (Am3+, Cm3+).
• Analysis of metal-coordinated water molecules and first-sphere/second-sphere interactions.

Main Results:

• Metal-coordinated water molecules enhance LanM's affinity and pH-stability for f-elements, contrary to small chelator behavior.
• The native aspartate residue hydrogen bonds to coordinated solvent rather than directly coordinating the metal.
• The asparagine variant nearly doubled LanM's selectivity for actinides over lanthanides by tuning these interactions.

Conclusions:

• Coordinated solvent plays an essential role in LanM's function for both physiological processes and separation applications.
• LanM's preference for actinides over lanthanides can be significantly improved through targeted modifications.
• Biomolecular scaffolds offer tunable interactions for developing advanced separation methods and bio-engineered chelators for medical isotopes.