6QA0

MSRB3 - AA 1-137

Summary for 6QA0

• Entry DOI: 10.2210/pdb6qa0/pdb
• Descriptor: Methionine-R-sulfoxide reductase B3, SULFATE ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: enzyme, methionine sulfoxide, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 32105.51

Authors

Javitt, G.,Fass, D. (deposition date: 2018-12-18, release date: 2020-01-15, Last modification date: 2024-11-13)

Primary citation

Javitt, G.,Cao, Z.,Resnick, E.,Gabizon, R.,Bulleid, N.J.,Fass, D.
Structure and Electron-Transfer Pathway of the Human Methionine Sulfoxide Reductase MsrB3.
Antioxid.Redox Signal., 33:665-678, 2020

PubMed Abstract: The post-translational oxidation of methionine to methionine sulfoxide (MetSO) is a reversible process, enabling the repair of oxidative damage to proteins and the use of sulfoxidation as a regulatory switch. MetSO reductases catalyze the stereospecific reduction of MetSO. One of the mammalian MetSO reductases, MsrB3, has a signal sequence for entry into the endoplasmic reticulum (ER). In the ER, MsrB3 is expected to encounter a distinct redox environment compared with its paralogs in the cytosol, nucleus, and mitochondria. We sought to determine the location and arrangement of MsrB3 redox-active cysteines, which may couple MsrB3 activity to other redox events in the ER. We determined the human MsrB3 structure by using X-ray crystallography. The structure revealed that a disulfide bond near the protein amino terminus is distant in space from the active site. Nevertheless, biochemical assays showed that these amino-terminal cysteines are oxidized by the MsrB3 active site after its reaction with MetSO. This study reveals a mechanism to shuttle oxidizing equivalents from the primary MsrB3 active site toward the enzyme surface, where they would be available for further dithiol-disulfide exchange reactions. Conformational changes must occur during the MsrB3 catalytic cycle to transfer oxidizing equivalents from the active site to the amino-terminal redox-active disulfide. The accessibility of this exposed disulfide may help couple MsrB3 activity to other dithiol-disulfide redox events in the secretory pathway.

PubMed: 32517586
DOI: 10.1089/ars.2020.8037

Experimental method

X-RAY DIFFRACTION (1.709 Å)