3u4d

Crystal structure of YwfH, NADPH dependent reductase involved in Bacilysin biosynthesis

spinqualitylabelsall models 3u4d, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u4d is a 1 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BACG_BACSU Along with the bacABCDEF operon, BacG is involved in the biosynthesis of the nonribosomally synthesized dipeptide antibiotic bacilysin, composed of L-alanine and L-anticapsin. Bacilysin is an irreversible inactivator of the glutaminase domain of glucosamine synthetase (PubMed:20052993). BacG catalyzes the stereoselective reduction of exocyclic-delta(3),delta(5)-dihydro-hydroxyphenylpyruvate (ex-H2HPP), adding a pro-S hydride equivalent to C4 position to yield tetrahydro-hydroxyphenylpyruvate (H4HPP) (PubMed:22765234, PubMed:23519407). Although the 3Z,7R-ex-H2HPP isomer is kinetically disfavored by BacB and produced in a smaller quantity than 3E,7R-ex-H2HPP, it is the preferred substrate for the conjugate reduction reaction of BacG (PubMed:22765234, PubMed:23519407). Publication Abstract from PubMed 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. Structural insights into the role of Bacillus subtilis YwfH (BacG) in tetrahydrotyrosine synthesis.,Rajavel M, Perinbam K, Gopal B Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):324-32. doi:, 10.1107/S0907444912046690. Epub 2013 Feb 16. PMID:23519407 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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