3ri6

Publication Abstract from PubMed

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 catalyzes the conversion of O-acetylhomoserine to homocysteine using sulfide in a process known as direct sulfhydrylation. However, the source of the sulfur has not been identified and no structures of OAHS have been reported in the literature. Here, the crystal structure of Wolinella succinogenes OAHS (MetY) determined at 2.2 A resolution is reported. MetY crystallized in space group C2 with two monomers in the asymmetric unit. Size-exclusion chromatography, dynamic light scattering and crystal packing indicate that the biological unit is a tetramer in solution. This is further supported by the crystal structure, in which a tetramer is formed using a combination of noncrystallographic and crystallographic twofold axes. A search for structurally homologous proteins revealed that MetY has the same fold as cystathionine gamma-lyase and methionine gamma-lyase. The active sites of these enzymes, which are also PLP-dependent, share a high degree of structural similarity, suggesting that MetY belongs to the gamma-elimination subclass of the Cys/Met metabolism PLP-dependent family of enzymes. The structure of MetY, together with biochemical data, provides insight into the mechanism of sulfur transfer to a small molecule via a protein thiocarboxylate intermediate.

A novel mechanism of sulfur transfer catalyzed by O-acetylhomoserine sulfhydrylase in the methionine-biosynthetic pathway of Wolinella succinogenes.,Tran TH, Krishnamoorthy K, Begley TP, Ealick SE Acta Crystallogr D Biol Crystallogr. 2011 Oct;67(Pt 10):831-8. Epub 2011, Sep 8. PMID:21931214^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.