Acta Crystallographica Section D

Biological Crystallography

Volume 69, Part 3 (March 2013)

research papers

Acta Cryst. (2013). D69, 324-332    [ doi:10.1107/S0907444912046690 ]

Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis

M. Rajavel, K. Perinbam and B. Gopal

Abstract: The synthesis of the dipeptide antibiotic bacilysin involves the sequential action of multiple enzymes in the bac operon. YwfH (also referred to as BacG) catalyzes the stereoselective reduction of dihydro-hydroxyphenylpyruvate (H2HPP) to tetrahydro-hydroxyphenylpyruvate (H4HPP) in this biosynthetic pathway. YwfH is an NADPH-dependent reductase that facilitates the conjugate addition of a hydride at the C4 olefin terminus of H2HPP. Here, the structure of YwfH is described at three conformational steps: the apo form, an apo-like conformation and the NADPH complex. YwfH is structurally similar to other characterized short-chain dehydrogenase/reductases despite having marginal sequence similarity. The structures of YwfH in different conformational states provide a rationale for the ping-pong reaction mechanism. The identification and role of the residues in the catalytic tetrad (Lys113-Tyr117-Ser155-Asn158) in proton transfer were examined by mutational analysis. Together, the structures and biochemical features revealed synchronized conformational changes that facilitate cofactor specificity and catalysis of H4HPP formation en route to tetrahydrotyrosine synthesis.

PDB references: 3u49, 3u4c and 3u4d

Keywords: short-chain dehydrogenase/reductases; bac operon; tetrahydro-hydroxyphenylpyruvate synthesis; tetrahydrotyrosine.

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