Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism

Nature Chemical Biology
Daniel P DowlingCatherine L Drennan

Abstract

7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg(2+)-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5'-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg(2+), which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified (β6/α3) protein core and an expanded cluster-binding motif, CX14CX2C.

References

Mar 5, 1987·Journal of Molecular Biology·A GoldmanT A Steitz
May 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P A Frey
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 13, 2001·Journal of Molecular Biology·H WaldenG L Taylor
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Aug 28, 2002·Biochemical Society Transactions·J FrazzonD R Dean
Jan 23, 2003·Bioinformatics·Charles S Bond
Jan 6, 2004·Science·Frederick BerkovitchCatherine L Drennan
Jun 9, 2004·Biochemical and Biophysical Research Communications·Hisanori TakagiMakoto Kimura
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 20, 2006·Molecular Microbiology·Christina ParaskevopoulouSilvia Onesti
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
May 16, 2006·Acta Crystallographica. Section D, Biological Crystallography·Marjorie M Harding
Mar 21, 2007·Methods : a Companion to Methods in Enzymology·Joanne C Cheung, Reinhart A F Reithmeier
Nov 17, 2007·Nature Protocols·Axel T Brunger
Jul 11, 2008·Journal of Inorganic Biochemistry·Heping ZhengWladek Minor
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jessica L VeyCatherine L Drennan
Oct 28, 2008·Nature Chemical Biology·Abhishek ChatterjeeSteven E Ealick
Mar 10, 2009·Current Opinion in Chemical Biology·Kaitlin S DuscheneJoan B Broderick
May 26, 2009·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerLi Wei Hung
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 9, 2010·Nature·Gunnar F SchröderAxel T Brunger
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Jun 4, 2010·The Journal of Biological Chemistry·Naoki ShibataTetsuo Toraya
Jul 27, 2010·Bioinformatics·Christian T LopesGary D Bader
Mar 5, 2011·Chemical Reviews·Jessica L Vey, Catherine L Drennan
Mar 26, 2011·Biochimica Et Biophysica Acta·Perry A Frey, George H Reed
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Mar 3, 2012·Bioorganic Chemistry·Reid M McCarty, Vahe Bandarian
Apr 21, 2012·Biochimica Et Biophysica Acta·E Neil G Marsh, Gabriel D Román Meléndez
May 15, 2012·Biochimica Et Biophysica Acta·Daniel P DowlingCatherine L Drennan
Nov 13, 2012·Current Opinion in Structural Biology·Krista A Shisler, Joan B Broderick
Sep 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Peter J GoldmanCatherine L Drennan
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

❮ Previous
Next ❯

Citations

Mar 16, 2016·Accounts of Chemical Research·Sarah E J BowmanCatherine L Drennan
Apr 23, 2016·Nature Chemistry·Roman RohacYvain Nicolet
Mar 31, 2015·Nature Communications·Michael K FenwickSteven E Ealick
Dec 13, 2016·RNA Biology·Geoffrey HutinetValérie de Crécy-Lagard
Jan 4, 2017·Journal of the American Chemical Society·Nathan A BruenderVahe Bandarian
Mar 28, 2017·Nature·Jennifer Bridwell-RabbHung-Wen Liu
Dec 24, 2014·Biochimica Et Biophysica Acta·Satoshi Kimura, Tsutomu Suzuki
Dec 28, 2016·Photochemistry and Photobiology·Olivier Berteau, Alhosna Benjdia
Mar 1, 2018·Physical Chemistry Chemical Physics : PCCP·Jessica BameAnna K Croft
Feb 28, 2018·Natural Product Reports·Mark W RuszczyckyHung-Wen Liu
Nov 20, 2018·Natural Product Reports·Lauren J Rajakovich, Emily P Balskus
Jun 22, 2018·Annual Review of Biochemistry·Jennifer Bridwell-RabbCatherine L Drennan
Dec 6, 2014·The Journal of Biological Chemistry·Tsehai A J GrellCatherine L Drennan
Feb 12, 2020·Journal of Bacteriology·Ben TurnerDirk Iwata-Reuyl
Aug 12, 2015·Journal of Biochemistry·Naoki Shibata, Tetsuo Toraya
Dec 6, 2014·The Journal of Biological Chemistry·Linlin Yang, Lei Li
Nov 20, 2016·Chemistry : a European Journal·Christof M Jäger, Anna K Croft
Feb 17, 2021·International Journal of Biological Macromolecules·Shunlin JiBochu Wang
Feb 23, 2020·Current Opinion in Chemical Biology·Wei DingQi Zhang
Jun 30, 2021·Biochemistry·Anthony P Young, Vahe Bandarian
Jul 10, 2021·RNA Biology·Katharina SieversRalf Ficner
Jan 31, 2014·Chemical Reviews·Joan B BroderickEric M Shepard
Jan 6, 2018·Journal of the American Chemical Society·Jarett WilcoxenR David Britt
Nov 16, 2019·Journal of Chemical Information and Modeling·Christian J SuessChristof M Jäger
May 25, 2018·Journal of the American Chemical Society·Tsehai A J GrellVahe Bandarian
Jul 10, 2019·Journal of the American Chemical Society·Sven A Miller, Vahe Bandarian

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

ccp4
PRISM
PyMOL
HKL2000
COOT
phenix
TOP
autoSHARP
Cytoscape
TLS Motion Determination Server

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.