The histidine brace: nature's copper alternative to haem?

• Published in: FEBS letters Vol. 597; no. 4; pp. 485 - 494
• Main Authors: Walton, Paul H., Davies, Gideon J., Diaz, Daniel E., Franco‐Cairo, João P.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.02.2023
• Subjects: copper; Copper - metabolism; haem; Heme - metabolism; Histidine - metabolism; histidine brace; LPMOs; Oxidation-Reduction; haem; LPMOs; copper; histidine brace
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14579

The copper histidine brace is a structural unit in metalloproteins (Proc Natl Acad Sci USA 2011, 108, 15079). It consists of a copper ion chelated by the NH2 and π‐N atom of an N‐terminal histidine, and the τ‐N atom of a further histidine, in an overall T‐shaped coordination geometry (Nat Catal 2018, 1, 571). Like haem‐containing proteins, histidine‐brace‐containing proteins have peroxygenase and/or oxygenase activity, where the substrates are notable for resistance to oxidation, for example, lytic polysaccharide monooxygenases (LPMOs). Moreover, the histidine brace is an invariant unit around which different protein structures exert different activities. Given the similarities in the diversity of function of proteins that contain either the copper histidine brace or haem, the question arises as to whether the functions of histidine brace‐containing proteins duplicate those containing haem groups. The histidine brace and haem groups show similarities between different proteins: structural invariance but both supporting a range of different functions.