Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP

Biochemistry
Kyle D Miner, Donald M Kurtz

Abstract

HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our result...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jun 28, 2003·FEMS Microbiology Reviews·Simon C AndrewsFrancisco Rodríguez-Quiñones
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Nov 5, 2005·The Journal of Chemical Physics·Wei Wang, Robert D Skeel
Apr 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Robert P RyanJ Maxwell Dow
Mar 17, 2009·Nature Reviews. Microbiology·Regine Hengge
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Robert P RyanJ Maxwell Dow
Aug 10, 2010·Journal of Molecular Biology·Anatoli TchigvintsevAlexander F Yakunin
Jun 1, 2011·Nucleic Acids Research·Aurélien GrosdidierOlivier Michielin
Nov 10, 2011·The Journal of Biological Chemistry·Michael Y Galperin, Eugene V Koonin
Mar 9, 2013·Microbiology and Molecular Biology Reviews : MMBR·Ute RömlingMark Gomelsky
Nov 19, 2013·Molecular Microbiology·Edvard WigrenUte Römling
Aug 28, 2014·The Journal of Biological Chemistry·James A Imlay
Sep 6, 2014·Current Pharmaceutical Design·Delphine L CalyRobert P Ryan
Oct 11, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·M S WeissL D Shea
Dec 2, 2014·Metallomics : Integrated Biometal Science·J-M Latour
Jan 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·TuAnh Ngoc HuynhJoshua J Woodward
Aug 13, 2015·The Journal of Biological Chemistry·Eleftheria TrampariJacob G Malone

❮ 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.