Mechanistic Insights into Dimethylsulfoniopropionate Lyase DddY, a New Member of the Cupin Superfamily

Chun-Yang Li, Dian Zhang, Xiu-Lan Chen, Peng Wang, Wei-Ling Shi, Ping-Yi Li, Xi-Ying Zhang, Qi-Long Qin, Jonathan D. Todd, Yu-Zhong Zhang

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The marine osmolyte dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur molecules. Bacterial DMSP lyases cleave DMSP, producing acrylate and dimethyl sulfide (DMS), a climate-active gas with roles in global sulfur cycling and atmospheric chemistry. DddY is the only known periplasmic DMSP lyase and is present in β-, γ-, δ- and ε-proteobacteria. Unlike other known DMSP lyases, DddY has not been classified into a protein superfamily, and its structure and catalytic mechanism are unknown. Here, we determined the crystal structure of DddY from the γ-proteobacterium Acinetobacter bereziniae originally isolated from human clinical specimens. This structure revealed that DddY contains a cap domain and a catalytic domain with a Zn2 + bound at its active site. We also observed that the DddY catalytic domain adopts a typical β-barrel fold and contains two conserved cupin motifs. Therefore, we concluded that DddY should belong to the cupin superfamily. Using structural and mutational analyses, we identified key residues involved in Zn2 + coordination, DMSP binding and the catalysis of DMSP cleavage, enabling elucidation of the catalytic mechanism, in which the residue Tyr271 of DddY acts as a general base to attack DMSP. Moreover, sequence analysis suggested that this proposed mechanism is common to DddY proteins from β-, γ-, δ- and ε-proteobacteria. The DddY structure and proposed catalytic mechanism provide a better understanding of how DMSP is catabolized to generate the important climate-active gas DMS.
Original languageEnglish
Pages (from-to)3850-3862
Number of pages13
JournalJournal of Molecular Biology
Issue number24
Early online date26 Oct 2017
Publication statusPublished - 8 Dec 2017


  • DMSP
  • catalytic mechanism
  • cupin superfamily
  • DMS generation
  • DMSP lyase DddY

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