Structural and catalytic differences between two FADH(2)-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134

Robert P Hayes; Brian N Webb; Arun Kumar Subramanian; Mark Nissen; Andrew Popchock; Luying Xun; Chulhee Kang

doi:10.3390/ijms13089769

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Structural and catalytic differences between two FADH(2)-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134

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Structural and catalytic differences between two FADH(2)-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134

Robert P Hayes, Brian N Webb, Arun Kumar Subramanian, Mark Nissen, Andrew Popchock, Luying Xun and Chulhee Kang

International journal of molecular sciences, Vol.13(8), pp.9769-9784

2012

DOI: https://doi.org/10.3390/ijms13089769

Handle:

https://hdl.handle.net/2376/111133

PMID: 22949829

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Abstract

Amino Acid Sequence

Models, Molecular

Molecular Sequence Data

Substrate Specificity

Crystallography, X-Ray

Flavin-Adenine Dinucleotide - analogs & derivatives

Mixed Function Oxygenases - metabolism

Mixed Function Oxygenases - chemistry

Sequence Homology, Amino Acid

Flavin-Adenine Dinucleotide - metabolism

Burkholderia cepacia - enzymology

Protein Conformation

Cupriavidus necator - enzymology

Catalysis

Chlorophenols - metabolism

2,4,5-TCP 4-monooxygenase (TftD) and 2,4,6-TCP 4-monooxygenase (TcpA) have been discovered in the biodegradation of 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP). TcpA and TftD belong to the reduced flavin adenine dinucleotide (FADH(2))-dependent monooxygenases and both use 2,4,6-TCP as a substrate; however, the two enzymes produce different end products. TftD catalyzes a typical monooxygenase reaction, while TcpA catalyzes a typical monooxygenase reaction followed by a hydrolytic dechlorination. We have previously reported the 3D structure of TftD and confirmed the catalytic residue, His289. Here we have determined the crystal structure of TcpA and investigated the apparent differences in specificity and catalysis between these two closely related monooxygenases through structural comparison. Our computational docking results suggest that Ala293 in TcpA (Ile292 in TftD) is possibly responsible for the differences in substrate specificity between the two monooxygenases. We have also identified that Arg101 in TcpA could provide inductive effects/charge stabilization during hydrolytic dechlorination. The collective information provides a fundamental understanding of the catalytic reaction mechanism and the parameters for substrate specificity. The information may provide guidance for designing bioremediation strategies for polychlorophenols, a major group of environmental pollutants.

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Title: Structural and catalytic differences between two FADH(2)-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134
Creators: Robert P Hayes - Department of Chemistry, Washington State University, Pullman, WA 99164, USA; E-Mails: robert_hayes@wsu.edu (R.P.H.); brian.webb1@email.wsu.edu (B.N.W.); subramanianarunk@gmail.com (A.K.S.); mnissen@wsu.edu (M.N.)
Brian N Webb
Arun Kumar Subramanian
Mark Nissen
Andrew Popchock
Luying Xun
Chulhee Kang
Publication Details: International journal of molecular sciences, Vol.13(8), pp.9769-9784
Academic Unit: Chemistry, Department of; Molecular Biosciences, School of
Publisher: Switzerland
Identifiers: 99900547202401842
Language: English
Resource Type: Journal article