How Zn²⁺ ion Affects the Structure of the Neurokinin A (NKA)?

Neurokinin A (NKA) is a neuropeptide which is a part of large class of molecules that play important biological functions in the brain. Zinc is known to be released from neurons during neuronal activity. It is hypothesized that NKA has the ability to bind zinc ions. In the current study, we examine the Zn²⁺-binding site in NKA and its effect on the structure of NKA.

Using molecular dynamics simulations, we found that in absence of zinc there NKA has a helical conformation (Figure 1a) which can transform between two further conformations that also have properties of helical structure in the central domain of the peptide and disordered structure in the termini. However, in absence of zinc ion the NKA has a wide range of conformations, i.e. a large conformational change along the potential energy surface. The wide range of the conformations of Zn²⁺-NKA are partially helical and/or disordered. One of the representative conformation is seen in Figure 1b. Interestingly, the zinc ion is hopping between two binding sites: oxygen atoms in the C-terminal of NKA and the imidazole nitrogen and the amine group of His1. Our results showed that the most preferred binding site is the His1, Asp4 and two water molecules that complete the coordination.

Figure 1: Representative structural models of NKA (sequence: HKTDSFVGLM) in absence of zinc ion (a) and in presence of zinc ion (b).