5YVO

Human Glutathione Transferase Omega1 covalently bound to ML175 inhibitor

Summary for 5YVO

• Entry DOI: 10.2210/pdb5yvo/pdb
• Descriptor: Glutathione S-transferase omega-1, SULFATE ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: inhibitor, gst, allosteric, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 28682.50

Authors

Saisawang, C.,Ketterman, A.,Wongsantichon, J. (deposition date: 2017-11-27, release date: 2018-11-28, Last modification date: 2024-11-06)

Primary citation

Saisawang, C.,Wongsantichon, J.,Robinson, R.C.,Ketterman, A.J.
Glutathione transferase Omega 1-1 (GSTO1-1) modulates Akt and MEK1/2 signaling in human neuroblastoma cell SH-SY5Y.
Proteins, 87:588-595, 2019

PubMed Abstract: In the human neuroblastoma SH-SY5Y cell line, the glutathione transferase Omega 1-1 (GSTO1-1) appears to modulate Akt and MEK1/2 kinase activation. We observed a glutathionylation modification was involved in the activation of Akt but not MEK1/2. With the specific GSTO1-1 inhibitor ML175, we show the enzyme activity of GSTO1-1 is important for modulation as the inhibited GSTO1-1 allowed activation of both Akt and MEK1/2. The inhibition of GSTO1-1 showed a similar extent of activation of Akt and MEK1/2 as treatment by the endotoxin lipopolysaccharide. The GSTO1-1 also either directly interacts with Akt and MEK1/2 or interacts with a protein complexed with Akt and MEK1/2 as both kinases coimmunoprecipitated with GSTO1-1. The results suggest that GSTO1-1 enzyme activity inhibits the activation of these two kinases to maintain basal levels. The possible regulation by GSTO1-1 is of interest as both kinases have hundreds of potential downstream targets that are known to have contributions to various cellular processes including survival, growth, proliferation, and metabolism.

PubMed: 30874320
DOI: 10.1002/prot.25683

Experimental method

X-RAY DIFFRACTION (1.8 Å)