Steve Ealick's Research Group

Wolinella succinogenes O-Acetylhomoserine Sulfhydrylase

PDB file:



O-acetylhomoserine sulfhydrylase (OAHS) is a pyridoxal 5´-phosphate (PLP)-dependent, sulfide-utilizing enzyme in the L-cysteine and L-methionine biosynthetic pathways of various enteric bacteria and fungi. OAHS has the same fold as cystathionine gamma lyase and methionine gamma lyase and its active site shares a high degree of structural similarity. This suggests that OAHS belongs to the γ-elimination subclass of the Cys/Met metabolism PLP-dependent family of enzymes. Our structure, coupled with biochemical data, provides insight into the mechanism of sulfur transfer to a small molecule via a protein thiocarboxylate intermediate.

The OAHS monomer adopts an α/β fold and is divided into two domains. The larger domain contains the PLP binding site and the seven-stranded β-sheet. The smaller domain is the capping domain near the C-terminal end. The monomer is quite compact due to tight packing between the two domains.

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While there are two monomers in the asymmetric unit, based on size exclusion chromatography and dynamic light scattering, as well as the PISA server, OAHS adopts a tetramer in the biologically active form.

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While no ligands were bound in our structure, the PLP cofactor, shown in cyan and red, could be modeled into the active site based on superposition of structural homologs. In our structure, this binding site was occupied by water molecules.

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Tran TH, Krishnamoorthy K, Begley TP and Ealick SE. A Novel Mechanism of Sulfur Transfer Catalyzed by O-Acetylhomoserine Sulfhydrylase in the Methionine Biosynthetic Pathway of Wolinella succinogene. Acta Cryst. D. 167:831-838 (2011). PubMed

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