In enzymes the "1st coordination sphere" describes the binding of substrate(s) to the active site whereas protein ligands that serve to correctly orient substrate(s) are generally defined as belonging to the "2nd coordination sphere". Protein elements that are found beyond that point, and still can affect catalysis, are part of the "outer coordination sphere". Quinolinate synthase is a good example of this classification because, besides having an active site and residues that accommodates its substrates, it modulates its catalytic site volume through remarkable internal conformational changes.
Quinolinate synthase : an example of the roles of the second and outer coordination spheres in enzyme catalysis. Juan C. Fontecilla-Camps* and Anne Volbeda. Chem Rev. (2022) doi : 10.1021/acs.chemrev.1c00869.
Contact : Juan Carlos Fontecilla-Camps (IBS/Metalloproteins group)