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. 2020 Jul 8;11:1011. doi: 10.3389/fphar.2020.01011

Figure 1.

Figure 1

ODSH localization and function in a macrophage cell line. ODSH is taken up by a mouse macrophage cell line (RAW264.7) into the cytoplasm within 2 h and into the nucleus by 24 h (Zheng et al., 2017) (A). ODSH has anti-NE activity and blocks HMGB1-RAGE interaction in the extracellular domain, and inhibits p300 lysine acetyltransferase activity in the nucleus (A). ODSH inhibits NE activity by binding to an allosteric inhibitory site (Kummarapurugu et al., 2018), and ODSH inhibits p300 enzyme activity by binding to the acetyl-CoA binding site in the catalytic domain (Zheng et al., 2017) (B). In contrast, ODSH binds to the loop connecting the A-box and B-box of HMGB1, blocking interaction with heparan sulfate proteoglycans required for HMGB1 ligation of the RAGE receptor (Xu et al., 2011) (B). Amino acid residues required for ODSH or heparin inhibitory activity are shown (Red Box).