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Streptomyces wadayamensis MppP is a PLP-Dependent Oxidase, Not an Oxygenase

Journal Article · · Biochemistry
 [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of Wisconsin, Milwaukee, WI (United States)
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The PLP-dependent l-arginine hydroxylase/deaminase MppP from Streptomyces wadayamensis (SwMppP) is involved in the biosynthesis of l-enduracididine, a nonproteinogenic amino acid found in several nonribosomally produced peptide antibiotics. SwMppP uses only PLP and molecular oxygen to catalyze a 4-electron oxidation of l-arginine to form a mixture of 2-oxo-4(S)-hydroxy-5-guanidinovaleric acid and 2-oxo-5-guanidinovaleric acid. Steady-state kinetics analysis in the presence and absence of catalase shows that one molecule of peroxide is formed for every molecule of dioxygen consumed in the reaction. Moreover, for each molecule of 2-oxo-4(S)-hydroxy-5-guanidinovaleric acid produced, two molecules of dioxygen are consumed, suggesting that both the 4-hydroxy and 2-keto groups are derived from water. This was confirmed by running the reactions using either [18]O2 or H2[18]O and analyzing the products by ESI-MS. Incorporation of [18]O was only observed when the reaction was performed in H2[18]O. Crystal structures of SwMppP with l-arginine, 2-oxo-4(S)-hydroxy-5-guanidinovaleric acid, or 2-oxo-5-guanidinovaleric acid bound were determined at resolutions of 2.2, 1.9. and 1.8 Å, respectively. The structural data show that the N-terminal portion of the protein is disordered unless substrate or product is bound in the active site, in which case it forms a well-ordered helix that covers the catalytic center. This observation suggested that the N-terminal helix may have a role in substrate binding and/or catalysis. Our structural and kinetic characterizations of N-terminal variants show that the N-terminus is critical for catalysis. Here, in light of this new information, we have refined our previously proposed mechanism of the SwMppP-catalyzed oxidation of l-arginine.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; National Science Foundation; USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1479015
Journal Information:
Biochemistry, Journal Name: Biochemistry Journal Issue: 23 Vol. 57; ISSN 0006-2960
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
Pyridoxal 5’-phosphate
chemical structure
enduracididine
hydroxylase
molecules
nonproteinogenic amino acid
oxygen
peptides and proteins
quinonoid
secondary metabolism
surface interactions