The protein GUSB, also known as β-glucuronidase, is a lysosomal enzyme crucial for the degradation of glycosaminoglycans (GAGs) [1]. GUSB plays a central role in the remodeling of extracellular matrix components in both physiological and inflammatory states [1]. It is a lysosomal homotetramer involved in the breakdown of glycosaminoglycans [2]. The enzyme is required for the degradation of dermatan and keratan sulphates [3]. GUSB is also involved in the deconjugation and activation of compounds such as curcumin-glucuronide in bone [4]. Furthermore, GUSB is a potential therapeutic protein for antibody-directed enzyme pro-drug therapy or enzyme replacement therapy of mucopolysaccharidosis type VII (MPS VII) [5]. The enzyme activity of GUSB has been observed in various regions of the brain, indicating its significance in brain function [6].
In addition, GUSB has been the subject of genetic studies, with mutations in the GUSB gene leading to diseases such as mucopolysaccharidosis VII in cats and severe skeletal abnormalities in Brazilian terriers [7]. The structure of the GUSB monomeric enzyme is well conserved among species, indicating its fundamental role across different organisms [7]. Moreover, GUSB has been implicated in the activation of Dectin-2-reporter cells, suggesting its involvement in immune responses [8]. The enzyme has also been engineered as a fusion protein with antibodies, demonstrating its potential for targeted therapy [9].
References:
[1] J. Sánchez, M. Bonet, J. Keijer, E. Schothorst, I. Mölller, C. Chetritet al., "Blood cells transcriptomics as source of potential biomarkers of articular health improvement: effects of oral intake of a rooster combs extract rich in hyaluronic acid", Genes & Nutrition, vol. 9, no. 5, 2014. https://doi.org/10.1007/s12263-014-0417-3
[2] M. Hytönen, M. Arumilli, A. Lappalainen, H. Kallio, M. Snellman, K. Sainioet al., "A novel gusb mutation in brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis vii", Plos One, vol. 7, no. 7, p. e40281, 2012. https://doi.org/10.1371/journal.pone.0040281
[3] R. Mydin, M. Alam, S. Sreekantan, K. Saharudin, E. Qazem, R. Hazanet al., "Mechano‐cytoskeleton remodeling mechanism and molecular docking studies on nanosurface technology: titania nanotube arrays", Biotechnology and Applied Biochemistry, vol. 70, no. 3, p. 1072-1084, 2023. https://doi.org/10.1002/bab.2421
[4] A. Kunihiro, P. Luis, J. Brickey, J. Frye, H. Chow, C. Schneideret al., "Beta-glucuronidase catalyzes deconjugation and activation of curcumin-glucuronide in bone", Journal of Natural Products, vol. 82, no. 3, p. 500-509, 2019. https://doi.org/10.1021/acs.jnatprod.8b00873
[5] X. Gao and L. Gan, "Receptor-mediated endocytosis and brain delivery of therapeutic biologics", International Journal of Cell Biology, vol. 2013, p. 1-14, 2013. https://doi.org/10.1155/2013/703545
[6] Y. Zhang, Y. Wang, R. Boado, & W. Pardridge, "Lysosomal enzyme replacement of the brain with intravenous non-viral gene transfer", Pharmaceutical Research, vol. 25, no. 2, p. 400-406, 2007. https://doi.org/10.1007/s11095-007-9357-6
[7] P. Wang, J. Sorenson, S. Strickland, C. Mingus, M. Haskins, & U. Giger, "Mucopolysaccharidosis vii in a cat caused by 2 adjacent missense mutations in the gusb gene", Journal of Veterinary Internal Medicine, vol. 29, no. 4, p. 1022-1028, 2015. https://doi.org/10.1111/jvim.13569
[8] D. Mori, K. Shibata, & S. Yamasaki, "C-type lectin receptor dectin-2 binds to an endogenous protein β-glucuronidase on dendritic cells", Plos One, vol. 12, no. 1, p. e0169562, 2017. https://doi.org/10.1371/journal.pone.0169562
[9] R. Boado and W. Pardridge, "Genetic engineering of igg-glucuronidase fusion proteins", Journal of Drug Targeting, vol. 18, no. 3, p. 205-211, 2009. https://doi.org/10.3109/10611860903353362
