Structural basis for divergent C-H hydroxylation selectivity in two Rieske oxygenases.

Nature Communications
April L LukowskiAlison R H Narayan

Abstract

Biocatalysts that perform C-H hydroxylation exhibit exceptional substrate specificity and site-selectivity, often through the use of high valent oxidants to activate these inert bonds. Rieske oxygenases are examples of enzymes with the ability to perform precise mono- or dioxygenation reactions on a variety of substrates. Understanding the structural features of Rieske oxygenases responsible for control over selectivity is essential to enable the development of this class of enzymes for biocatalytic applications. Decades of research has illuminated the critical features common to Rieske oxygenases, however, structural information for enzymes that functionalize diverse scaffolds is limited. Here, we report the structures of two Rieske monooxygenases involved in the biosynthesis of paralytic shellfish toxins (PSTs), SxtT and GxtA, adding to the short list of structurally characterized Rieske oxygenases. Based on these structures, substrate-bound structures, and mutagenesis experiments, we implicate specific residues in substrate positioning and the divergent reaction selectivity observed in these two enzymes.

References

Oct 15, 1975·Journal of the American Chemical Society·J BordnerH Rapoport
Jul 25, 1991·Nucleic Acids Research·R H DonJ S Mattick
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Nov 7, 1996·Chemical Reviews·Bradley J. Wallar, John D. Lipscomb
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 12, 2005·Journal of Molecular Biology·Hideaki NojiriToshio Omori
Sep 20, 2005·Biochemical and Biophysical Research Communications·Daniel J FerraroS Ramaswamy
Oct 21, 2005·Journal of Bacteriology·Lokesh GakharS Ramaswamy
Mar 31, 2006·Natural Product Reports·Lyndon E Llewellyn
Jun 5, 2007·Accounts of Chemical Research·Carsten KrebsJ Martin Bollinger
Sep 13, 1968·Science·D T Gilbson
Sep 23, 2009·Acta Crystallographica. Section D, Biological Crystallography·Nigel W MoriartyPaul D Adams
Oct 16, 2009·Accounts of Chemical Research·Toshitaka MatsuiMasao Ikeda-Saito
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Gábor Bunkóczi, Randy J Read
Jun 10, 2011·The Journal of Biological Chemistry·Mahmood MohammadiMichel Sylvestre
Dec 29, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jenna K Capyk, Lindsay D Eltis
May 4, 2012·Nucleic Acids Research·Karel BerkaMichal Otyepka
Sep 17, 2013·ELife·Andrew MorinPiotr Sliz
Nov 19, 2013·ACS Catalysis·Sarah M Barry, Gregory L Challis
Jan 10, 2014·Chemical Reviews·Thomas L Poulos
Apr 29, 2014·Angewandte Chemie·Arun P ThottumkaraJ Du Bois
May 30, 2015·Journal of the American Chemical Society·David M WithallGregory L Challis
Mar 10, 2016·Journal of Bacteriology·Sonali DhindwalPravindra Kumar
May 4, 2016·Journal of the American Chemical Society·John V MulcahyJ Du Bois
Oct 30, 2016·Biochemistry·Edward I SolomonKyle D Sutherlin
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Feb 9, 2017·Journal of Chemical Information and Modeling·Diego E EscalanteAlptekin Aksan

❮ Previous
Next ❯

Citations

Jan 9, 2021·Current Opinion in Biotechnology·Remi ZallotJohn A Gerlt
Feb 19, 2021·Nature Communications·Peter M HeinemannBernhard Hauer
Feb 19, 2021·Accounts of Chemical Research·Suman ChakrabartyAlison R H Narayan
Jul 31, 2020·Current Opinion in Chemical Biology·Jonathan R ChekanBradley S Moore
Aug 5, 2021·ACS Central Science·Joshua B PyserAlison R H Narayan
Dec 8, 2021·The Journal of Organic Chemistry·Doris T Y TangJ Du Bois

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
gel filtration

Software Mentioned

MOLEonline
COOT
HKL2000
PyMol
Phenix
DALI
SxtT
Excel
SBGrid
Phenix AutoMR

Related Concepts

Related Feeds

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Related Papers

Biochemical and Biophysical Research Communications
Daniel J FerraroS Ramaswamy
Biochimica Et Biophysica Acta
D Schneider, C Schmidt
© 2022 Meta ULC. All rights reserved