Beta-carotene hydroxylase (CrtR), the carotenoid zeaxanthin biosynthetic enzyme catalyzes the addition of hydroxyl groups to the beta-ionone rings of beta-carotene to form zeaxanthin and is found in bacteria and red algae. Carotenoids are important natural pigments; zeaxanthin and lutein are the only dietary carotenoids that accumulate in the macular region of the retina and lens. It is proposed that these carotenoids protect ocular tissues against photooxidative damage. CrtR does not show overall amino acid sequence similarity to the beta-carotene hydroxylases similar to CrtZ, an astaxanthin biosynthetic beta-carotene hydroxylase. However, CrtR does show sequence similarity to the green alga, Haematococcus pluvialis, beta-carotene ketolase (CrtW), which converts beta-carotene to canthaxanthin. Sequences of the CrtR_beta-carotene-hydroxylase domain family, as well as, the CrtW_beta-carotene-ketolase domain family appear to be structurally related to membrane fatty acid desaturases and alkane hydroxylases. They all share in common extensive hydrophobic regions that would be capable of spanning the membrane bilayer at least twice. Comparison of these sequences also reveals three regions of conserved histidine cluster motifs that contain eight histidine residues: HXXXH, HXXHH, and HXXHH. These histidine residues are reported to be catalytically essential and proposed to be the ligands for the iron atoms contained within homologs, stearoyl CoA desaturase and alkane hydroxylase.
Jiyao W et al.(2023). "The conserved domain database in 2023.",