BIOCHEMISTRY: Analyzing the Structure & Function of D-Glucuronyl

This report delves into the structural and functional aspects of D-Glucuronyl C5-epimerase, a primary enzyme involved in Heparin sulfate (HS) synthesis. It highlights the enzyme's role in converting D-glucuronic acid to L-iduronic acid, which is crucial for increasing HS flexibility. The report emphasizes the importance of HS in various physiological processes, including inflammatory response, blood coagulation, cell growth, and viral infections, due to its ability to bind to a variety of proteins. It discusses the enzyme's catalytic sites, tyrosine residues essential for enzymatic activity, and mechanisms of inhibition, such as sulfation of HS. The report also explains the C5-epimerization reaction and its significance in maximizing the flexibility of heparin sulfate for cell signaling and ligand recognition.

Running head: BIOCHEMISTRY 1
Structure and Function of D-Glucuronyl C5-epimerase
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BIOCHEMISTRY 2
D-Glucuronyl C5-epimerase is one of the primary enzymes responsible for Heparin
sulfate (HS) synthesis through the conversion of D-glucuronic acid to L-iduronic acid for the
purpose of increasing HS flexibility(Qin et al. 2015). HS is one of the glycosaminoglycans
present in the extracellular matrix and cell surface which interact with many signal molecules
and its crucial for diverse physiological processes. All animal cells tissues contain key proteins
that are covalently attached to each other by the HS chain. HS, being negatively charged
polysaccharide is capable of binding to a variety of proteins including chemokines, growth
factors and interleukins(Qin et al. 2015). Due to that fact, HS regulates a number of biological
and physiological processes including inflammatory response, blood coagulation, cell growth,
tumor metastasis, embryonic development and viral infections(Raedts et al. 2013).
The structural structure of D-Glucuconyl C5-epimerase contains two catalyst sites at
which each is positively charged in C-terminal alpha-helical domains. These positively charged
terminals usually bid to negatively charged hexasaccharides(Qin et al. 2015). In addition, D-
Glucuronic D5-epimerase has three tyrosine residues which include Tyr528, Tyr468, and Tyr456
in the active site which are essential for enzymatic activity. The structure of D-Glucuronic D5-
epimerase also shows some mechanism of inhibition(Qin et al. 2015). For instance, 6-0- and 2-0-
sulfation of HS usually keeps the C5 of L-iduronic acid away from the tyrosine residues active
site. The synthesis and conversion of D-glucuronic acid to L-iduronic acid is done through C5-
epimerization reaction(Qin et al. 2015). The epimerization reaction normally maximizes the
flexibility of heparin sulfate and it is important for the function of HS in cell signaling and ligand
recognition(Qin et al. 2015).

BIOCHEMISTRY 3
References
Qin, Yi, Jiyuan Ke, Xin Gu, Jianping Fang, Wucheng Wang, Qifei Cong, Jie Li, et al. 2015.
“Structural and Functional Study of D-Glucuronyl C5-Epimerase.” Journal of Biological
Chemistry. https://doi.org/10.1074/jbc.M114.602201.
Raedts, John, Magnus Lundgren, Servé W.M. Kengen, Jin-Ping Li, and John Van Der Oost.
2013. “A Novel Bacterial Enzyme with D-Glucuronyl C5-Epimerase Activity.” Journal of
Biological Chemistry. https://doi.org/10.1074/jbc.M113.476440.