6SSR

Crystal structure of Human Microsomal Glutathione S-Transferase 2 at 3.8 Angstroms resolution

Summary for 6SSR

• Entry DOI: 10.2210/pdb6ssr/pdb
• Descriptor: Microsomal glutathione S-transferase 2 (1 entity in total)
• Functional Keywords: er membrane protein, glutathione transferase, mapeg, mgst2, integral membrane enzyme, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 52396.23

Authors

Thulasingam, M.,Nji, E.,Rinaldo-Matthis, A.,Haeggstrom, J.Z. (deposition date: 2019-09-09, release date: 2021-02-03, Last modification date: 2024-01-24)

Primary citation

Thulasingam, M.,Orellana, L.,Nji, E.,Ahmad, S.,Rinaldo-Matthis, A.,Haeggstrom, J.Z.
Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis.
Nat Commun, 12:1728-1728, 2021

PubMed Abstract: Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets.

PubMed: 33741927
DOI: 10.1038/s41467-021-21924-8

Experimental method

X-RAY DIFFRACTION (3.8 Å)