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

Leader, D. P. and Milner-White, E. J. (2023) The conserved crown bridge loop at the catalytic centre of enzymes of the haloacid dehalogenase superfamily. Current Research in Structural Biology, 6, 100105. (doi: 10.1016/j.crstbi.2023.100105) (PMID:37786806) (PMCID:PMC10541634)

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-αRαR crown bridge loop — found in approximately 7% of proteins — and the 2,3-βRαL 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-βRαL 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-βRαL conformation — but not the 2,3-αRαR conformation — allows the backbone carbonyl group at position 2 to interact with the essential Mg2+ ion. The possibility of interconversion between the 2,3-βRαL and 2,3-αRαR conformations during catalysis is discussed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leader, Dr David and Milner-White, Professor E
• Authors: Leader, D. P., and Milner-White, E. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Current Research in Structural Biology
• Publisher: Elsevier
• ISSN: 2665-928X
• ISSN (Online): 2665-928X
• Published Online: 18 September 2023
• Copyright Holders: Copyright © 2023 The Authors.
• First Published: First published in Current Research in Structural Biology 6:100105
• Publisher Policy: Reproduced under a Creative Commons license