Metal–ligand interactions: An analysis of zinc binding groups using the Protein Data Bank

In the present study, we investigated zinc binding groups (ZBGs) using the coordinates of protein–ligand complex structures obtained from the Protein Data Bank. The distance from the zinc to the nearest ligand atom was measured to determine whether the atom was part of the ZBG. The most frequently found ZBG was carboxylate, followed by sulfonamide, hydroxamate, and phosphonate/phosphate. Because it was found that few heteroatoms, such as nitrogen, oxygen, and sulfur atoms, interacted with zinc, ideal distances between the zinc and these heteroatoms were identified. Whereas carboxylates bound to the zinc via both monodentate and bidentate interactions, the hydroxamates bound dominantly in a bidentate manner. These results will aid in the design of new inhibitors with the potential to interact with zinc in the target protein.

Graphical abstractA database of zinc binding groups (ZBGs) was developed using coordinates obtained from the Protein Data Bank. In addition, Zn-ZBG interactions were analyzed to help the design of new ZBGs.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Zinc metalloproteins contain many drug targets. ► ZBGs are important for the inhibition of the enzymes. ► Many ZBGs were identified and classified. ► Details of the coordination of ZBGs were described. ► A Method to design new inhibitors by the replacement of the ZBG moiety was proposed.