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

Rajavel, Malligarjunan and Perinbam, Kumar and Gopal, B (2013) Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis. In: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 69 (3). pp. 324-332.

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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 (Lys113Tyr117Ser155Asn158) 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.

Item Type:	Journal Article
Publication:	ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Publisher:	WILEY-BLACKWELL
Additional Information:	Copyright for this article belongs to the WILEY-BLACKWELL, USA.
Keywords:	short-chain dehydrogenase; reductases; bac operon; tetrahydro-hydroxyphenylpyruvate synthesis; tetrahydrotyrosine
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	14 May 2013 07:59
Last Modified:	14 May 2013 07:59
URI:	http://eprints.iisc.ac.in/id/eprint/46496

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