YHR049w/FSH1, a member of the serine hydrolase family

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The structure of FSH1.
(A) Ribbon representation of FSH1. Helices, strands, and loops are colored blue, pink, and orange, respectively. Insertions relative to the canonical alpha/beta-hydrolase fold are colored green (cap) and beige (beta-sheet beta5-beta6). The catalytic triad residues (Ser110, His218, and Asp183) are shown as sticks. (B) Superimposition of the P. fluorescens carboxylesterase (yellow, PDB code 1AUR) structure on the S. cerevisiae FSH1 protein (same color code as Fig. 1A). Residues of the catalytic triads as well as the molecules covalently bound to FSH1 and carboxylesterase catalytic Ser are shown as sticks. (C) Stereo view of the 2Fo-Fc electron density map contoured at 1sigma (blue). The molecule covalently bound to Ser110 has been omitted for calculation of this map. For clarity, the map is only drawn around the Ser110 residue. This density was modeled by a phosphoester compound (P atom in green). Dotted lines depict potential hydrogen of the bound compound.

Function Putative serine hydrolase, might be an esterase
Fold ?/? hydrolase fold
Resolution 1.7
Remark Catalytic serine
PDB code Not yet
Publication Quevillon-Cheruel S, Leulliot N, Graille M, Hervouet N, Coste F, Benedetti H, Zelwer C, Janin J, Van Tilbeurgh H. Crystal structure of yeast YHR049W/FSH1, a member of the serine hydrolase family.Protein Sci. 2005 May;14(5):1350-6. Full text

Yhr049w/FSH1 was recently identified in a combined computational and experimental proteomics analysis for the detection of active serine hydrolases in yeast. This analysis suggested that FSH1 might be a serine-type hydrolase belonging to the broad functional alphabeta-hydrolase superfamily. In order to get insight into the molecular function of this gene, it was targeted in our yeast structural genomics project. The crystal structure of the protein confirms that it contains a Ser/His/Asp catalytic triad that is part of a minimal alpha/beta-hydrolase fold. The architecture of the putative active site and analogies with other protein structures suggest that FSH1 may be an esterase. This finding was further strengthened by the unexpected presence of a compound covalently bound to the catalytic serine in the active site. Apparently, the enzyme was trapped with a reactive compound during the purification process.