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

Journal Article · · Biochemistry
 [1];  [1];  [1];  [1];  [1]; ORCiD logo [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 Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE; Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; National Science Foundation (NSF)
Grant/Contract Number:
AC02-06CH11357; 085P1000817; CHE-1606842
OSTI ID:
1479015
Journal Information:
Biochemistry, Vol. 57, Issue 23; ISSN 0006-2960
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

References (40)

The membrane-associated form of methane mono-oxygenase from Methylococcus capsulatus (Bath) is a copper/iron protein journal January 2003
X-ray Crystal Structure of Escherichia coli Taurine/α-Ketoglutarate Dioxygenase Complexed to Ferrous Iron and Substrates † , ‡ journal April 2002
Flavin Mono-Oxygenase (FMO) - The ‘Other’ Oxidase journal May 2008
O 2 - and α-Ketoglutarate-Dependent Tyrosyl Radical Formation in TauD, an α-Keto Acid-Dependent Non-Heme Iron Dioxygenase † journal February 2003
Crystallization and preliminary crystallographic analysis of maganese(II)-dependent 2,3-dihydroxybiphenyl 1,2-dioxygenase from Bacillus sp. JF8 journal February 2010
Manganese(II)-Dependent Extradiol-Cleaving Catechol Dioxygenase from Arthrobacter globiformis CM-2 † journal January 1996
Revisiting Heme Mechanisms. A Perspective on the Mechanisms of Nitric Oxide Synthase (NOS), Heme Oxygenase (HO), and Cytochrome P450s (CYP450s) journal February 2008
Structural insights into catalysis by βC-S lyase from Streptococcus anginosus: Structure Analysis of S. anginosus βC-S Lyase journal July 2012
Crystal Structure at 1.45 Å Resolution of Alanine Racemase from a Pathogenic Bacterium, Pseudomonas aeruginosa , Contains Both Internal and External Aldimine Forms , journal November 2003
Crystal structure of Saccharomyces cerevisiae cytosolic aspartate aminotransferase journal June 1998
Mammalian dopa decarboxylase: Structure, catalytic activity and inhibition journal March 2014
High resolution structure and catalysis of O-acetylserine sulfhydrylase isozyme B from Escherichia coli: Structure of the O-acetylserine sulfhydrylase CysM journal September 2007
Mechanism of Radical-based Catalysis in the Reaction Catalyzed by Adenosylcobalamin-dependent Ornithine 4,5-Aminomutase journal December 2008
Tyrosine 70 fine-tunes the catalytic efficiency of aspartate aminotransferase journal July 1991
Lysine 258 in aspartate aminotransferase: Enforcer of the Circe effect for amino acid substrates and the general-base catalyst for the 1,3-prototropic shift journal February 1993
PLP and PMP Radicals: A New Paradigm in Coenzyme B6 Chemistry journal August 2001
Insights into the Mechanism of Oxidative Deamination Catalyzed by DOPA Decarboxylase journal June 2008
Plant Phenylacetaldehyde Synthase Is a Bifunctional Homotetrameric Enzyme That Catalyzes Phenylalanine Decarboxylation and Oxidation journal June 2006
Streptomyces wadayamensis MppP Is a Pyridoxal 5′-Phosphate-Dependent l -Arginine α-Deaminase, γ-Hydroxylase in the Enduracididine Biosynthetic Pathway journal November 2015
A pyridoxal phosphate–dependent enzyme that oxidizes an unactivated carbon-carbon bond journal January 2016
Mannopeptimycins, a novel class of glycopeptide antibiotics active against gram-positive bacteria journal February 2005
Mannopeptimycins, New Cyclic Glycopeptide Antibiotics Produced by Streptomyces hygroscopicus LL-AC98: Antibacterial and Mechanistic Activities journal January 2003
Anti-Microbial Activities of Enduracidin (Enramycin) in Vitro and in vivo journal January 1971
In vitro and in vivo Activity of Enduracidin on Staphylococcus aureus journal January 1972
Teixobactin: A Novel Antibiotic in Treatment of Gram Positive Bacterial Infections journal January 2015
The manifold of vitamin B6 dependent enzymes journal January 2000
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM journal March 2011
Phaser crystallographic software journal July 2007
Overview of the CCP 4 suite and current developments journal March 2011
Joint X-ray and neutron refinement with phenix.refine journal October 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Features and development of Coot journal March 2010
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation 1 1Edited by J. Thornton journal January 1999
Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions journal November 2004
X-Ray Crystallographic Study of Pyridoxal 5′-Phosphate-Type Aspartate Aminotransferases from Escherichia coli in Open and Closed Form1 journal July 1994
POVScript+ : a program for model and data visualization using persistence of vision ray-tracing journal May 2003
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures journal October 1991
Structural and Functional Characterization of MppR, an Enduracididine Biosynthetic Enzyme from Streptomyces hygroscopicus : Functional Diversity in the Acetoacetate Decarboxylase-like Superfamily journal June 2013
Importance of spontaneous α-ketoacid decarboxylation in experiments involving peroxide journal August 1990

Cited By (4)

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Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi journal December 2019

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Related Subjects

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