Spodium Bonds in Biological Systems: Expanding the Role of Zn in Protein Structure and Function.

Himansu S Biswal,Akshay Kumar Sahu,Antonio Frontera,Antonio Bauzá

doi:10.1021/acs.jcim.1c00594

Abstract

Understanding the structural and functional implications of metal ions is of pivotal significance to chemical biology. Herein, we report first time the evidence of spodium bonds (SpB’s, an attractive noncovalent force involving elements from group 12 and electron-rich species) in tetrahedral Zn-binding sites. Through a combined crystallographic (PDB analysis) and computational (ab initio calculations) study, we demonstrate that Zn SpB’s are abundant and might be involved in protein structure and enzyme inhibition.

Highlights

During the last decade, noncovalent interactions (NCIs) have starred a fast growing revolution which have led them to become essential resources of the chemist toolbox owing to their crucial role in several fields of modern chemistry, such as supramolecular chemistry,[1] molecular recognition,[2] and materials science.[3]
Despite of the great importance that hydrogen-bonding (HB) interactions play in many chemical and biological systems,[4,5] such as in enzymatic chemistry and protein folding and binding phenomena,[6] other NCIs based on the p-block of elements [aerogen (Ae),[7] halogen (Hal),[8] chalcogen (Ch),[9] pnictogen (Pn),[10] and tetrel (Tr) bonds]11 have emerged during the last decade
If the bond paths are arranged as to enclose the interior of a molecule with ring surfaces, a (3, +3) cage critical point is found in the interior of the cage, the interactions (A = N, O, and S, see Supporting Information for detailed information regarding search criteria and statistical data) are shown, revealing a total number of 52,758 contacts

Summary

Introduction

Noncovalent interactions (NCIs) have starred a fast growing revolution which have led them to become essential resources of the chemist toolbox owing to their crucial role in several fields of modern chemistry, such as supramolecular chemistry,[1] molecular recognition,[2] and materials science.[3] Despite of the great importance that hydrogen-bonding (HB) interactions play in many chemical and biological systems,[4,5] such as in enzymatic chemistry and protein folding and binding phenomena,[6] other NCIs based on the p-block of elements [aerogen (Ae),[7] halogen (Hal),[8] chalcogen (Ch),[9] pnictogen (Pn),[10] and tetrel (Tr) bonds]11 have emerged during the last decade This family of interactions is known as “σ-hole bonding”. Zn2+ is one of the most important trace metal ions and an essential cofactor in many metabolic enzymes and regulatory proteins.[21−23] Zn2+ can play a catalytic role acting as a Lewis acid (i.e., an electron pair acceptor), facilitating deprotonation of Zn-coordinated water in human carbonic anhydrase II (HCA2)[24] or stabilizing negatively charged intermediate species, such as in carboxypeptidase A.25 On the other hand, Zn2+ ions play a fundamental role in protein structure and folding, such as in Zn-finger proteins.[26]

Methods

Results

Conclusion