4D7L

Methionine sulfoxide reductase A of Corynebacterium diphtheriae

Summary for 4D7L

• Entry DOI: 10.2210/pdb4d7l/pdb
• Descriptor: PEPTIDE METHIONINE SULFOXIDE REDUCTASE MSRA, CACODYLATE ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, thiol disulfide exchange
• Biological source: CORYNEBACTERIUM DIPHTHERIAE NCTC 13129
• Total number of polymer chains: 3
• Total formula weight: 82083.92

Authors

Van Molle, I.,Tossounian, M.A.,Pedre, B.,Wahni, K.,Vertommen, D.,Messens, J. (deposition date: 2014-11-25, release date: 2015-03-18, Last modification date: 2024-10-23)

Primary citation

Tossounian, M.,Pedre, B.,Wahni, K.,Erdogan, H.,Vertommen, D.,Van Molle, I.,Messens, J.
Corynebacterium Diphtheriae Methionine Sulfoxide Reductase a Exploits a Unique Mycothiol Redox Relay Mechanism.
J.Biol.Chem., 290:11365-, 2015

PubMed Abstract: Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

PubMed: 25752606
DOI: 10.1074/JBC.M114.632596

Experimental method

X-RAY DIFFRACTION (1.895 Å)