Structural and Functional Studies of a Pyran Synthase Domain from a trans-Acyltransferase Assembly Line

ACS Chemical Biology
Drew T WagnerAdrian T Keatinge-Clay

Abstract

trans-Acyltransferase assembly lines possess enzymatic domains often not observed in their better characterized cis-acyltransferase counterparts. Within this repertoire of largely unexplored biosynthetic machinery is a class of enzymes called the pyran synthases that catalyze the formation of five- and six-membered cyclic ethers from diverse polyketide chains. The 1.55 Å resolution crystal structure of a pyran synthase domain excised from the ninth module of the sorangicin assembly line highlights the similarity of this enzyme to the ubiquitous dehydratase domain and provides insight into the mechanism of ring formation. Functional assays of point mutants reveal the central importance of the active site histidine that is shared with the dehydratases as well as the supporting role of a neighboring semiconserved asparagine.

References

Mar 31, 2004·The Journal of Biological Chemistry·M Kristian KoskiTuomo Glumoff
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Aug 28, 2007·Chemistry & Biology·Adrian T Keatinge-Clay
Jul 5, 2008·Nature Protocols·Gerrit LangerAnastassis Perrakis
Oct 28, 2008·Journal of Molecular Biology·Adrian Keatinge-Clay
Apr 14, 2009·Nature Methods·Daniel G GibsonHamilton O Smith
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
May 14, 2010·Natural Product Reports·Jörn Piel
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Jan 17, 2012·Applied and Environmental Microbiology·Lei ShaoJixun Zhan
Aug 4, 2012·Natural Product Reports·Adrian T Keatinge-Clay
Sep 21, 2013·Nature·Tom BretschneiderChristian Hertweck
Dec 7, 2013·Angewandte Chemie·Petra PöplauJörn Piel
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Aug 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Alessandra S EustáquioFrank E Koehn
Aug 4, 2015·Nature Chemical Biology·Reiko UeokaJörn Piel
Sep 18, 2015·Angewandte Chemie·Hanna LuhavayaPeter F Leadlay
Nov 20, 2015·Natural Product Reports·Adrian T Keatinge-Clay
Dec 23, 2015·Natural Product Reports·Eric J N Helfrich, Jörn Piel
Jan 16, 2016·Chembiochem : a European Journal of Chemical Biology·Matthew J BertinWilliam H Gerwick
Dec 15, 2016·Journal of the American Chemical Society·William D FiersCourtney C Aldrich
Mar 23, 2017·Angewandte Chemie·Adrian T Keatinge-Clay
Apr 6, 2017·Journal of Molecular Biology·Alexandre FailleJean-Denis Pedelacq
Apr 11, 2017·Chemical Reviews·Adrian T Keatinge-Clay
Oct 31, 2017·Angewandte Chemie·Kwang Hoon SungFrank Hahn

❮ Previous
Next ❯

Citations

Jul 20, 2018·Antibiotics·Ewa Maria Musiol-Kroll, Wolfgang Wohlleben
Jun 14, 2018·Angewandte Chemie·Srividhya SundaramChristian Hertweck
Oct 4, 2018·Natural Product Reports·Simone KosolGregory L Challis
Oct 13, 2018·Natural Product Reports·Akimasa Miyanaga
Dec 10, 2020·Journal of Natural Products·Raha OrfaliOrazio Taglialatela-Scafati

❮ Previous
Next ❯

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.