The conserved crown bridge loop at the catalytic centre of enzymes of the haloacid dehalogenase superfamily

David P Leader; E James Milner-White

doi:10.1016/j.crstbi.2023.100105

The conserved crown bridge loop at the catalytic centre of enzymes of the haloacid dehalogenase superfamily

Curr Res Struct Biol. 2023 Sep 18:6:100105. doi: 10.1016/j.crstbi.2023.100105. eCollection 2023.

Authors

David P Leader¹, E James Milner-White¹

Affiliation

¹ College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.

Abstract

The crown bridge loop is hexapeptide motif in which the backbone carbonyl group at position 1 is hydrogen bonded to the backbone imino groups of positions 4 and 6. Residues at positions 1 and 4-6 are held in a tight substructure, but different orientations of the plane of the peptide bond between positions 2 and 3 result in two conformers: the 2,3-α_Rα_R crown bridge loop - found in approximately 7% of proteins - and the 2,3-β_Rα_L crown bridge loop, found in approximately 1-2% of proteins. We constructed a relational database in which we identified 60 instances of the 2,3-β_Rα_L conformer, and find that about half occur in enzymes of the haloacid dehalogenase (HAD) superfamily, where they are located next to the catalytic aspartate residue. Analysis of additional enzymes of the HAD superfamily in the extensive SCOPe dataset showed this crown bridge loop to be a conserved feature. Examination of available structures showed that the 2,3-β_Rα_L conformation - but not the 2,3-α_Rα_R conformation - allows the backbone carbonyl group at position 2 to interact with the essential Mg²⁺ ion. The possibility of interconversion between the 2,3-β_Rα_L and 2,3-α_Rα_R conformations during catalysis is discussed.