Current Research

Metallostasis: Transition metal homeostasis in bacterial pathogens (project 1)

In this project, our goal is to understand the molecular mechanisms of how cells regulate the intracellular bioavailability of essential transition metal ions, notably Cu, Mn and Zn among others. This process, termed metal homeostasis and resistance, represents an important battleground in human host-bacterial pathogen interactions since these ions may be limiting or in excess, both detrimental to the survival of the invading microbe. Metal sensor proteins bind specific DNA sequences and regulate the expression of homeostasis genes in response to specific metal ions. Recent studies involve the use of ion mobility mass spectrometry and methyl-NMR dynamics approaches to elucidate mechanisms of allosteric regulation in metallosensors, and understanding the physiological response of Acinetobacter baumanni to host-imposed Zn limitation, Fe limitation and Mn toxicity in Streptococcus pneumoniae using a variety of analytical approaches.

Persulfide sensing and reactive sulfur species (RSS) in bacteria (project 2)

In this project, we are developing new concepts of bacterial hydrogen sulfide (H2S) homeostasis, and seeking an understanding of the chemistry and physiological adaptation of H2S misregulation in important microbial pathogens.  In 2014, we discovered a paralog of a copper-sensing operon repressor CsoR in Staphylococcus aureus that we coined CstR, for CsoR-like sulfurtransferase repressor. CstR senses reactive sulfur species (RSS), including inorganic and organic low molecular weight (LMW) thiol persulfides, that result from the effects of sulfide stress, resulting in induction of the cst operon. Ongoing work in selected firmicutes and in Gram-negative bacteria (Rhodobacter, Acinetobacter spp.) reveals that RSS sensing and hydrogen sulfide homeostasis is more widespread than previously thought. We discovered orthogonal chemistries of two RSS-inducible enzymes that clear RSS and developed quantitative RSS profiling and a global proteomics workflow to detect S-sulfuration in bacteria. Current work is focused on the structural biology of RSS clearance systems and the deleterious impact of over-persulfidation in cells.

Metallostasis and H2S/RSS homeostasis are linked by the LMW thiol pool foundational to cellular redox and transition metal buffering, cysteine thiol chemistry, and iron-sulfur (Fe-S) protein biogenesis. Recent work suggests that a new (yet old!) LMW thiol/thione, L-ergothioneine, may be widespread in firmicutes, and is the “glue” that bridges both projects.


Reviews and Perspectives

Publications

2022

Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine
Zhang, Y., Gonzalez-Gutierrez, G., Legg, K. A., Edwards, K. A., and GIEDROC, D. P. (2022) BioRxiv, (doi: 10.1101/2022.05.02.490363) (under review)
View: BioRxiv

SifR is an Rrf2-family quinone sensor associated with iron-catechol uptake in Streptococcus pneumoniae D39
Zhang, Y., Martin, J. E., Edmonds, K. A., Winkler, M. E., and GIEDROC, D. P. (2022)
J. Biol Chem, in the press (doi: 10.1016/j.jbc.2022.102046). *Editor’s pick
View: PubMed

Protocol using cysteine persulfide to elucidate chemical reactivity of persulfide sensors
Fakhoury, J. N., Capdevila, D. A. and GIEDROC, D. P. (2022)
STAR Protoc 3, 101424 (doi: 10.1016/j.xpro.2022.101424)
View: PubMed

Zn regulated GTPase metalloprotein activator 1 (ZNG1) regulates zinc homeostasis in vertebrates
Weiss, A., Murdoch, C. C., Edmonds K. A., Jordan, M. R., Monteith, A. J., Perera, Y. R.,
Rodríguez Nassif, A. M., Petoletti, A. M., Beavers, W. N., Krystofiak, E. S., Thalluri, K., Wu, H., DiMarchi, R. D., Chazin, W. J., *GIEDROC, D. P., and *Skaar E. P. (2022)
Cell 185, 1-16 (doi: 10.1016/j.cell.2022.04.011)
View: PubMed

Bacterial hydrophilins promote pathogen desiccation tolerance
Green, E.R., Fakhoury, J.N., Monteith, A. J., Pi, H., GIEDROC, D.P. and Skaar, E.P. (2022)
Cell Host Microbe, S1931-3128(22)00149-4 (doi: 10.1016/j.chom.2022.03.019)
View: PubMed

2021

Functional asymmetry and chemical reactivity of CsoR family persulfide sensors
Fakhoury, J. N., Zhang, Y., Edmonds, K. A., Bringas, M., Luebke, J. L., Gonzalez-Gutierrez, G., Capdevila, D. A., and GIEDROC, D. P. (2021)
Nucl. Acid Res. 49, 12556-12576 (doi: 10.1093/nar/gkab1040)
View: PubMed

COG0523 proteins: A functionally diverse family of transition metal-regulated G3E P-loop GTP hydrolases from bacteria to man
Edmonds, K. A., Jordan, M. R., and GIEDROC, D. P. (2021)
Metallomics 13, mfab046 (doi: 10.1093/mtomcs/mfab046).
View: PubMed

Proteomics Profiling of S-sulfurated Proteins in Acinetobacter baumannii
Walsh, B. J. C., and GIEDROC, D. P. (2021)
Bio Protoc 11, e4000 (doi: 10.21769/BioProtoc.4000)
View: PubMed

Structural basis for persulfide-sensing specificity in a transcriptional regulator
Capdevila, D. A., Walsh, B. J. C., Zhang, Y., Dietrich, C., Gonzalez-Gutierrez, G., and GIEDROC, D. P. (2021)
Nat. Chem. Biol. 17, 65-70 (doi: 10.1038/s41589-020-00671-9)
View: PubMed

2020

Staphylococcus aureus glucose-induced biofilm accessory protein A (GbaA) is a monothiol-dependent electrophile sensor
Ray, A., Edmonds, K. A., Palmer, L. D., Skaar, E. P., and GIEDROC, D. P. (2020)
Biochemistry 59, 2882–2895 (doi: 10.1021/acs.biochem.0c00347).
View: PubMed

The response of Acinetobacter baumannii to hydrogen sulfide reveals two independent persulfide-sensing systems and a connection to biofilm regulation
Walsh, B.J.C., Wang, J., Edmonds, K. A., Palmer, L. D., Zhang, Y., Trinidad, J. C., Skaar, E. P., and GIEDROC, D. P. (2020)
mBio 11, e01254-20 (doi: 10.1128/mBio.01254-20).
View: PubMed

The pneumococcal iron uptake protein A (PiuA) specifically recognizes tetradentate Fe(III) bis– and mono-catechol complexes
Zhang, Y., Edmonds, K. A., Raines, D. J., Murphy, B. A., Wu, H., Guo, C., Nolan, E. M., VanNieuwenhze, M. S., Duhme-Klair, A.-K., GIEDROC, D. P. (2020)
J. Mol. Biol. 432, 5390-5410 (doi: 10.1016/j.jmb.2020.08.005).
View: Pubmed

1H, 13C, 15N backbone resonance assignments of the apo and holo forms of the ABC transporter solute binding protein PiuA from Streptococcus pneumoniae
Edmonds, K. A., Zhang, Y., Raines, D. J., Duhme-Klair, A.-K., and GIEDROC, D. P. (2020)
Biomolec. NMR Assign. 14, 233–238 (doi: 10.1007/s12104-020-09952-9).
View: Pubmed

Clostridioides difficile senses and hijacks host heme for incorporation into an oxidative stress defense system
Knippel, R. J., Wexler, A. G., Miller, J. M., Beavers, W. N., Weiss, A., de Crécy-Lagard, V., Edmonds, K. A., GIEDROC, D. P. and Skaar, E. P. (2020)
Cell Host Microbe 28, 411-421.e6 (doi: 10.1016/j.chom.2020.05.015)
View: Pubmed

Cell-free biosensors for detection of water contaminants
Jung, J. K., Alam, K. K., Verosloff, M. S., Capdevila, D. A., Desmau, M., Clauer, P. R., Lee, J. W., Nguyen, P. Q., Pasten, P. A., Matiasek, S., Gaillard, J.-F., GIEDROC, D. P., Collins, J. J., and Lucks, J. B. (2020)
Nat. Biotech. 38, 1451-1459 (doi.org/10.1038/s41587-020-0571-7).
View: Pubmed

2019

A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus
Martin, J. E., Le, M. T., Bhattarai, N., Capdevila, D. A., Shen, J., Winkler, M. E. and GIEDROC, D. P. (2019)
Nucl. Acids Res. 47, 6885–6899 (doi: 10.1093/nar/gkz494).
View: Pubmed

An Acinetobacter baumannii zinc regulated peptidase maintains cell wall integrity during immune-mediated nutrient sequestration
Lonergan, Z. R., Nairn, B. L., Wang, J., Hsu, Y.-P., Hesse, L. E., Beavers, W. N., Chazin, W. J., Trinidad, J. C., VanNieuwenhze, M. S., GIEDROC, D. P., and Skaar, E. P. (2019)
Cell Rep. 26, 2009-2018.e6. (doi:10.1016/j.celrep.2019.01.089).
View: Pubmed

Multi-metal restriction by calprotectin impacts de novo flavin biosynthesis in Acinetobacter baumannii
Wang, J., Lonergan, Z. R., Gonzalez-Gutierrez, G., Nairn, B. L., Maxwell, C. N., Zhang, Y., Andreini, C., Karty, J. A., Chazin, W. J., Trinidad, J. C., Skaar, E. P., and GIEDROC, D. P. (2019)
Cell Chem. Biol. 16, 745-755.e7. (doi: 10.1016/j.chembiol.2019.02.011).
View: Pubmed

Mechanistic insights into the metal-dependent activation of Zn(II)-dependent metallochaperones
Jordan, M. R., Wang, J., Weiss, A., Skaar, E. P., Capdevila, D. A., and GIEDROC, D. P. (2019)
Inorg. Chem. 58, 13661-13672 (doi: 10.1021/acs.inorgchem.9b01173).
View: Pubmed

2018

Thioredoxin profiling of multiple thioredoxin-like proteins in Staphylococcus aureus
Peng, H., Zhang, Y., Trinidad, J. C.,  & Giedroc, D. P. (2018)
Front. Microbiol. 9, 2385  (doi: 10.3389/fmicb.2018.02385)
View: PubMed

Hydrogen sulfide sensing through reactive sulfur species (RSS) and nitroxyl (HNO) in Enterococcus faecalis
Shen, J., Walsh, B. J. C., Flores-Mireles, A. L., Peng, H., Zhang, Y., Zhang, Y., Trinidad, J. C., Hultgren, S. J., & Giedroc, D. P. (2018)
ACS Chem. Biol. 13, 1610-1620 (doi: 10.1021/acschembio.8b00230)
View: PubMed

Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator
Capdevila, D. A., Huerta, F., Edmonds, K. A, Le, M. T., Wu, H. & GIEDROC, D. P. (2018)
eLife 7, e37268 (doi: 10.7554/eLife.37268)
View: Pubmed

Functional role of solvent entropy and conformational entropy of metal binding in dynamically driven allosteric system
Capdevila, D. A., Edmonds, K. A, Campanello, G. C., Wu, H., Gonzalez-Gutierrez G,. & GIEDROC, D. P. (2018)
J Am. Chem. Soc. 140, 9108-9119 (doi: 0.1021/jacs.8b02129)
View: Pubmed

2017

Hydrogen sulfide and reactive sulfur species impact S-sulfhydration and global virulence regulation in Staphylococcus aureus
Peng, H., Zhang, Y., Palmer, L, D., Kehl-Fie, T. E., Skaar, E. C., Trinidad, J. C., & Giedroc, D. P. (2017)
ACS Infect. Dis. 3, 744-755 (doi: 10.1021/acsinfecdis.7b00090)
View: PubMed

Sulfide homeostasis and nitroxyl intersect via formation of reactive sulfur species (RSS) in Staphylococcus aureus
Peng, H., Shen, J., Edmonds, K. A., Luebke, J. L., Hickey, A. K., Palmer, L, D., Cheng, F.-M.J., Bruce, K. A., Kehl-Fie, T. E., Skaar, E. C., & Giedroc, D. P. (2017)
mSphere 2e00082-17 (doi:10.1128/mSphere.00082-17) 
View: PubMed

The sulfide-responsive transcriptional repressor SqrR functions as a master regulator of sulfide-dependent photosynthesis
Shimizu, T., Shen, J., Fang, M., Zhang, Y., Hori, K., Trinidad, J. C., Bauer, C. E., Giedroc, D. P. and Masuda, S. (2017)
Proc. Natl. Acad. Sci. U.S.A. 114, 2355-2360 (doi: 10.1073/pnas.1614133114).
View: PubMed

Metal-dependent allosteric activation and inhibition on the same molecular scaffold: The copper sensor CopY from Streptococcus pneumoniae
Glauninger, H., Zhang, Y., Higgins, K. A., Jacobs, A. D., Martin, J. E., Fu, Y., H. Coyne, J. 3rd, Bruce, K. E., Maroney, M. J., Clemmer, D. E., Capdevila, D. A., & GIEDROC, D. P. (2017)
Chem. Sci. 9, 105-118 (doi: 10.1039/c7sc04396a)
View: Pubmed

Entropy redistribution controls allostery in a zinc metalloregulatory protein
Capdevila, D. A., Braymer, J. J., Edmonds, K. A., Wu, H., & GIEDROC, D. P. (2017)
Proc. Natl Acad. Sci. USA 114, 4424-4429 (doi: 10.1073/pnas.1620665114) 
View: Pubmed

See the Commentary by Josh Wand in Proc Natl Acad Sci USA

The pneumococcal zinc efflux activator SczA protects Streptococcus pneumoniae serotype 2 D39 from intracellular zinc toxicity
Martin, J. E., Edmonds, K. A., Bruce, K. E., Campanello, G. C., Eijkelkamp, B. A., Brazel, E. B., McDevitt, C. A., Winkler, M. E., & GIEDROC, D. P. (2017)
Mol. Microbiol. 104, 636-651 (doi: 10.1111/mmi.13654)
View: Pubmed

Perturbation of manganese metabolism disrupts cell division in Streptococcus pneumoniae
Martin, J. E. Lisher, J. P., Winkler, M. E., & GIEDROC, D. P. (2017)
Mol. Microbiol. 104, 334-348 (doi: 10.1111/mmi.13630).
View: Pubmed

Biological and chemical adaptation to endogenous hydrogen peroxide production in Streptococcus pneumoniae D39
Lisher, J. P., Ramos-Montañez, S., Hentchel, K. L. Tsui- T.-H., Winkler, M. E. & GIEDROC, D. P. (2017)
mSphere 2, e00291-16 (doi: 10.1128/mSphere.00291-16)
View: Pubmed

2016

Staphylococcus aureus sqr encodes a type II sulfide:quinone oxidoreductase (SQR) and impacts reactive sulfur speciation in cells
Shen, J., Peng, H., Zhang, Y., Trinidad, J. C., & Giedroc, D. P. (2016)
Biochemistry 55, 6524-6534
View: PubMed

The response of Acinetobacter baumannii to zinc starvation 
Nairn, B. L., Lonergan, Z. R., Wang, J., Braymer, J. J., Zhang, Y., Calcutt, M. W., Gilston, B. A, Chazin, W. J., de Crécy-Lagard, V., GIEDROC, D. P.*, & Skaar, E. P.*  (2016)
Cell Host Microbe 19, 826-836 (doi: 10.1016/j.chom.2016.05.007)
View: Pubmed

Functional determinants of metal ion transport and selectivity in paralogous cation diffusion facilitator transporters CzcD and MntE in Streptococcus pneumoniae
Martin, J. E., & GIEDROC, D. P. (2016)
J. Bacteriol. 198, 1066-1076 (doi: 10.1128/JB.00975-15)
View: Pubmed

Crystal structure of Clostridium difficile toxin
Rutherford, S. A., Chumber, N. M., Zhang, Z., Lisher, J. P., Farquhar, E., GIEDROC, D. P., Spiller, B. W.., Melnyk, R. A., and Lacy, D. B. (2016)
Nature Microbiol.1, article number 15002 (doi:10.1038/nmicrobiol.2015.2)
View: Pubmed

The S2 Cu(I) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance
Fu, Y., Bruce, K., Wu, H. & GIEDROC, D. P. (2016)
Metallomics 8, 61-70 (doi: 10.1039/c5mt00221d)
View: PubMed

2015

Staphylococcus aureus CstB is a novel multidomain persulfide dioxygenase-sulfurtransferase involved in hydrogen sulfide detoxification
Shen, J., Keithly, M. E., Armstrong, R. N., Higgins, K. A., Edmonds, K. A. & Giedroc, D. P. (2015)
Biochemistry 54, 4542-4554 (doi: 10.1021/acs.biochem.5b00584)
View: PubMed

Resolution of stepwise cooperativities of copper binding by the homotetrameric copper-sensitive operon repressor (CsoR): Impact on structure and stability
Jacobs, A.D., Chang, F.-M.J, Morrison, L., Dilger, J.M., Wysocki, V.H., Clemmer, D.E., & GIEDROC, D. P. (2015)
Angew. Chem. Int. Ed. 54, 1-6 (doi: 10.1002/anie.201506349)
View: PubMed

Electrostatic occlusion and quaternary structural ion pairing are key determinants of Cu(I)-mediated allostery in the copper-sensing operon repressor (CsoR)
Chang, F.-M.J., Martin, J.E. & GIEDROC, D. P. (2015)
Biochemistry 54, 2462-2473 (doi: 10.1021/acs.biochem.5b00154)
View: PubMed

Conformational analysis and chemical reactivity of the multidomain sulfurtransferase, Staphylococcus aureus CstA
Higgins, K. A., Peng, H., Luebke, J. L., Chang, F.-M. J., & Giedroc, D. P. (2015)
Biochemistry 54, 2385-2398 (doi: 10.1021/acs.biochem.5b00056)
View: PubMed

2014

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus.
Luebke, J. L., Shen, J., Bruce, K. E., Kehl-Fie, T. E., Peng, H., Skaar, E. P., & Giedroc, D. P. (2014)
Mol. Microbiol. 94, 1343-1360 (doi: 10.1111/mmi.12835)
View: PubMed

Cu(I)-mediated allosteric switching in a copper-sensing operon repressor (CsoR)
Chang, F.-M. J., Coyne, H.J., Cubillas, C., Vinuesa, P., Fang, X., Ma, Z., Ma, D., Helmann, J.D., Garcia-de los Santos, A., Wang, Y.X., Dann, C.E. & GIEDROC, D. P. (2014)
J. Biol. Chem 289, 19204-19217 (doi: 10.1074/jbc.M114.556704)
View: PubMed

Conversion of S-phenylsulfonylcysteine residues to mixed disulfides at pH 4.0: utility in protein thiol blocking and in protein-S-nitrosothiol detection
Reeves, B.D., Joshi, N., Campanello, G.C., Hilmer, J.K., Chetia, L., Vance, J.A., Reinschmidt, J.N., Miller, C.G., Dratz, E.A., Singel, D.J., Grieco, P.A. & GIEDROC, D. P. (2014)
Org. Biomol. Chem. 12, 7942-7956 (doi: 10.3389/fcimb.2013.00091)
View: PubMed

2013

Co-ordinate synthesis and protein localization in a bacterial organelle by the action of a penicillin-binding-protein
Hughes, H.V., Lisher, J.P., Hardy, G.G., Kysela, D.T., Arnold, R.J., Brun, Y.V., & GIEDROC, D. P. (2013)
Mol Microbiol 90, 1162-1177 (doi: 10.1111/mmi.12422)
View: PubMed

Physical characterization of the manganese-sensing pneumococcal surface antigen repressor from Streptococcus pneumoniae.
Lisher, J. P, Higgins, K. A., Maroney, M. J., & GIEDROC, D. P. (2013)
Biochemistry 52,7689-7701 (doi: 10.1021/bi401132w)
View: PubMed

Solution NMR refinement of a metal ion bound protein using metal ion inclusive restrained molecular dynamics methods.
Chakravorty, D. K, Wang, B., Lee, C. W., Guerra, A .J., GIEDROC, D. P., & Merz, K. M. Jr. (2013)
J. Biomol. NMR 56, 125-137.
View: PubMed

Selenite and tellurite form mixed seleno- and tellurotrisulfides with CstR from Staphylococcus aureus
Luebke, J. L., Arnold, R. A. & Giedroc, D. P. (2013)
Metallomics 5, 335-342 (doi: 10.1039/c3mt20205d)
View: PubMed

A new structural paradigm in copper resistance in Streptococcus pneumoniae.
Fu, Y., Tsui, H .-C., Bruce, K. E., Sham, L. T., Higgins, K. A., Lisher, J .P., Kazmierczak, K. M., Maroney, M. J., Dann, C. E. 3rd, Winkler, M. E., & GIEDROC, D. P. (2013)
Nat. Chem. Biol. 9, 177-183.
View: PubMed

Allosteric inhibition of a zinc-sensing transcriptional repressor: Insights into the arsenic repressor (ArsR) family.
Campanello, G. C., Ma, Z., Grossoehme, N. E., Guerra, A. J., Ward, B. P., Dimarchi, R. D., Ye, Y,, Dann, C. E., 3rd, & GIEDROC, D. P. (2013)
J. Mol. Biol. 425, 1143-1157.
View: PubMed

Energetics of zinc-mediated interactions in the allosteric pathways of metal sensor proteins.
Chakravorty, D. K., Parker, T. M., Guerra, A. J., Sherrill, C. D., GIEDROC, D. P., & Merz, K. M. Jr. (2013)
J. Am. Chem. Soc. 135, 30-33.
View: PubMed

2012

Backbone resonance assignments of the homotetrameric (48 kD) copper sensor CsoR from Geobacillus thermodenitrificans in the apo- and Cu(I)-bound states: insights into copper-mediated allostery.
Coyne, H. J., 3rd., & GIEDROC, D. P. (2012)
Biomol. NMR Assign. 7, 279-283 (doi: 10.1007/s12104-012-9428-4)
View: PubMed

(1)H, (13)C, and (15)N resonance assignments of NmtR, a Ni(II)/Co(II) metalloregulatory protein of Mycobacterium tuberculosis.
Lee, C. W., & GIEDROC, D. P. (2012)
Biomol. NMR Assign. 7, 145-148 (doi: 10.1007/s12104-012-9397-7)
View: PubMed

Solution structure of Mycobacterium tuberculosis NmtR in the apo state: insights into Ni(II)-mediated allostery.
Lee, C. W., Chakravorty, D. K., Chang, F. M., Reyes-Caballero, H., Ye, Y., Merz, K. M., Jr., GIEDROC, D. P. (2012)
Biochemistry 51, 2619-2629.
View: PubMed

Simulations of allosteric motions in the zinc sensor CzrA.
Chakravorty, D., Wang, B., Lee, C. W., GIEDROC, D. P., & Merz, K.M., Jr. (2012)
J. Am. Chem. Soc. 134, 3367-3376.
View: PubMed

Backbone and sterospecific methyl side chain resonance assignments of the homodimeric zinc sensor AdcR (32 kDa) in the apo- and Zn(II)-bound states.
Guerra, A. J.., & GIEDROC, D. P. (2012)
Biomol. NMR Assign. 8, 11-14 (doi: 10.1007/s12104-012-9442-6)
View: PubMed

2011

Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus
Grossoehme, N., Kehl-Fie, T.E., Ma, Z., Adams, K.W., Cowart, D.M., Scott, R.A., Skaar, E.P., & Giedroc, D.P. (2011)
J. Biol. Chem. 286, 13522-13531
View: PubMed

Mycobacterium tuberculosis NmtR harbors a nickel sensing site with parallels to Escherichia coli RcnR.
Reyes-Caballero, H., Lee, C. W., & GIEDROC, D. P. (2011)
Biochemistry 50, 7941-7952.
View: PubMed

Control of copper resistance and inorganic sulfur metabolism by paralogous regulators in Staphylococcus aureus.
Grossoehme, N. E., Kehl-Fie, T. E., Ma, Z., Adams, K. W., Cowart, D. M., Scott, R. A., Skaar, E. P. ,& GIEDROC, D. P. (2011)
J. Biol. Chem. 286, 13522-13531.
View: PubMed

Interplay between manganese and zinc homeostasis in the human pathogen Streptococcus pneumoniae.
Jacobsen, F. E., Kazmierczak, K. M., Lisher, J. P., Winkler, M. E., & GIEDROC, D. P. (2011)
Metallomics 3, 38-41.
View: PubMed

Crystal structure of the zinc-dependent MarR family transcriptional regulator AdcR in the Zn(II)-bound state.
Guerra, A. J., Dann, C. E., III, & GIEDROC, D. P.  (2011)
J. Am. Chem. Soc. 133, 19614-19617.
View: PubMed

Ratiometric pulse-chase amidination mass spectrometry as a probe of biomolecular complex formation.  
Chang, F.-M., Lauber, M. A., Running, W. E., Reilly, J. P., & GIEDROC, D. P.  (2011)
Anal. Chem. 83, 9092–9099.
View: PubMed

2010

The CRR1 Nutritional Copper Sensor in Chlamydomonas Contains Two Distinct Metal-Responsive Domains.
Sommer, F,. Kropat, J., Malasarn, D., Grossoehme, N. E., Chen, X., GIEDROC, D. P., Merchant, S. S. (2010)
Plant Cell 22, 4098-4113.
View: PubMed

The metalloregulatory zinc site in Streptococcus pneumoniae AdcR, a zinc-activated MarR family repressor.
Reyes-Caballero, H., Guerra, A. J., Jacobsen, F. E., Kazmierczak, K. M., Cowart, D., Koppolu, U. M., Scott, R. A., Winkler, M. E., & GIEDROC, D. P. (2010)
J. Mol. Biol. 403, 197-216.
View: PubMed

Elucidation of the functional metal binding profile of a Cd(II)/Pb(II) sensor CmtR(Sc).
Wang, Y., Kendall, J., Cavet, J. S., & GIEDROC, D. P. (2010)
Streptomyces coelicolor. Biochemistry 49, 6617-6626.
View: PubMed

2009

Molecular insights into the metal selectivity of the Cu(I)-sensing repressor CsoR from Bacillus subtilis.
Ma, Z., Cowart, D., Scott, R. A. & GIEDROC, D. P.  (2009)
Biochemistry 48, 3325-3334.
View: PubMed

Structure of Thermotoga maritima TM0439: Implications for the mechanism of bacterial GntR transcription regulators with Zn2+-binding FCD domains.
Zheng, M., Cooper, D. R., Grossoehme, N. E., Yu, M., Hung, L. W., Cieslik, M., Derewenda, U., Lesley, S. A, Wilson, I. A., GIEDROC, D. P., Derewenda, Z. S. (2009) 
Acta Cryst
 65, 356-365.
View: PubMed

Solution structure of a paradigm ArsR family sensor in the DNA bound state.
Arunkumar, A. I., Campanello, G. C. & GIEDROC, D. P.  (2009)
Proc. Natl. Acad. Sci. U. S. A. 106, 18177-18182.
View: PubMed

Energetics of allosteric negative coupling in the zinc sensor S. aureus CzrA.
Grossoehme, N. E., & GIEDROC, D. P. (2009)
J. Am. Chem. Soc. 131, 17860-17870.
View: PubMed

Unnatural amino acid substitution as a probe of the allosteric coupling pathway in a mycobacterial Cu(I) sensor.
Ma, Z., Cowart, D. M, Ward, B. P., Arnold, R. J., DiMarchi, R. D., Zhang, L., George, G. N., Scott, R. A., & GIEDROC, D. P. (2009)
J. Am. Chem. Soc. 131, 18044-18045.
View: PubMed

2008

A Cu(I)-sensing ArsR family metal sensor protein with a relaxed metal selectivity profile.
Liu, T., Chen, X., Ma, Z., Shokes, J., Hemmingsen, L, Scott, R. A., Giedroc, D. P. (2008)
Biochemistry 47, 10564-10575.
View: PubMed

Copper sensing by Drosophila metal-responsive transcription factor-1 requires a Cu(I)4-S6 cluster.
Chen, X., Hua, H., Balamurugan, K., Kong, X., Wang, L., George, G. N., Georgiev, O., Schaffner, W. and Giedroc, D. P. (2008)
Nucl. Acids Res., 36, 3128-3138.
View:

2007

Multiple metal-binding domains enhance the Zn(II) selectivity of the divalent metal ion transporter AztA.
Liu, T., Reyes, H., Li, C., Li, C., Scott, R. A., & Giedroc, D. P. (2007)
Biochemistry 46, 11057-11068.
View: PubMed

Resonance assignments of the metal sensor CzrA in the apo-, Zn2- and DNA-bound (42 kDa) states.
Arunkumar, A. I., Pennella, M. A., Kong, X., and Giedroc, D. P. (2007)
Biomol. NMR Assign 1, 99-101.
View:  SpringerLink

CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator.
Liu, T., Ramesh, A., Ma, Z, Ward, S. K., Zhang, L., George, G. N., Talaat, A. M., Sacchettini, J. C., & Giedroc, D. P. (2007)
Nature Chem. Biol. 3, 60-68.
View:  PubMed

2006

Individual Metal Ligands Play Distinct Functional Roles in the Zinc Sensor Staphylococcus aureus CzrA.
Pennella, M.A., Arunkumar, A.I., & Giedroc, D. P. (2006)
J. Mol. Biol. 356, 1124-1136.
View:  PubMed

Structural Insights into Homo- and Heterotropic Allosteric Coupling in the Zinc Sensor S. aureus CzrA from Covalently Fused Dimers.
Lee, S., Arunkumar, A.I., Chen, X., & Giedroc, D. P. (2006)
J. Am. Chem. Soc. 128, 1937-1947.
View:  PubMed

Kinetics of Metal Binding by the Toxic Metal-Sensing Transcriptional Repressor S. aureus pI258 CadC.
Busenlehner, L. S., and Giedroc, D. P. (2006)
J. Inorg. Biochem. 100, 1024-1034.
View: PubMed

1998-2005

A Zn(II)/Pb(II)/Cd(II)-Inducible Operon from Anabaena is Regulated by AztR, an alpha3N ArsR/SmtB-family Metalloregulator.
Liu, T., Golden, J. W., & Giedroc, D. P. (2005)
Biochemistry 44, 8673-8683.
View:  PubMed

Structural and Functional Characterization of M. tuberculosis CmtR, a Pb(II)/Cd(II)-sensing SmtB/ArsR Metalloregulatory Repressor.
Wang, Y., & Hemmingsen, L., & Giedroc, D. P. (2005)
Biochemistry 44, 8976-8988.
View:  PubMed

A Novel Cyanobacterial SmtB/ArsR Family Metalloregulator Regulates a CPx-ATPase and a Metallothionein in Response to both Cu(I)/Ag(I) and Zn(II)/Cd(II).
Liu, T., Nakashima, S., Hirose, K., Shibasaka, M., Katsuhara, M., Ezaki, B., Giedroc, D. P., & Kasamo, K. (2004)
J. Biol. Chem. 279, 17810-17818.
View:  PubMed

A Novel Cysteine Cluster in Human MTF-1 is Required for Heavy Metal-induced Transcriptional Activation in vivo.
Chen, X., Zhang, B., Harmon, P. M., Schaffner, W., Peterson, D. O., & Giedroc, D. P. (2004)
J. Biol. Chem. 279, 4515-4522.
View:  PubMed

Ratiometric Pulsed Alkylation-Mass Spectrometry as a Probe of Thiolate Reactivity in Different Metalloderivatives of S. aureus pI258 CadC.
Apuy, J. A., Busenlehner, L. S., Russell, D. H., & Giedroc, D. P. (2004)
Biochemistry 43, 3824-3834.
View:  PubMed

A Metal-Ligand mediated Intersubunit Allosteric Switch in Related SmtB/ArsR Zinc Sensor Proteins.
Eicken, C., Pennella, M. A., Chen, X., Koshlap, K., VanZile, M. L., Sacchettini, J. C., & Giedroc, D. P. (2003)
J. Mol. Biol. 333, 683-695.
View:  PubMed

Structural Elements of Metal Selectivity in Metal Sensor Proteins.
Pennella, M. A., Shokes, J. E., Cosper, N. J., Scott, R. A., & Giedroc, D. P. (2003)
Proc. Natl. Acad. Sci. USA 100, 3713-3718.
View:  PubMed

A Nickel-Cobalt Sensing ArsR-SmtB Family Repressor: Contributions of the Cytosol and Effector Binding Sites to Metal Selectivity.
Cavet, J. S., Meng, W., Pennella, M. A., Appelhoff, R. J., Giedroc, D. P., & Robinson, N. J. (2002)
J. Biol. Chem. 277, 38441-38448.
View:  PubMed

Allosteric Negative Regulation of smt O/P Binding of the Zinc Sensor, SmtB, by Metal Ions: A Coupled Equilibrium Analysis.
VanZile, M. L., Chen, X., & Giedroc, D. P. (2002)
Biochemistry 41, 9776-9786.
View:  PubMed

Structural and Functional Characterization of a Metalloregulatory Bi(III) Site in S. aureus pI258 CadC.
Busenlehner, L. S., Apuy, J. L., & Giedroc, D. P. (2002)
J. Biol. Inorg. Chem. 7, 551-559.
View:  PubMed

Elucidation of Primary (alpha3N) and Vestigial (alpha5) Heavy Metal Binding Sites in S. aureus pI258 CadC: Evolutionary Implications for Metal Ion Selectivity of ArsR/SmtB Metal Sensor Proteins.
Busenlehner, L. S., Weng, T. -C., Penner-Hahn, J. E. & Giedroc, D. P. (2002)
J. Mol. Biol. 319, 685-701.
View:  PubMed

Structural Characterization of Distinct alpha3N and alpha5 Metal Sites in the Cyanobacterial Zinc Sensor SmtB.
VanZile, M.L., Chen, X., & Giedroc, D.P. (2002)
Biochemistry 41, 9765-9775.
View:  PubMed

Spectroscopic Properties of the Metalloregulatory Cd(II) and Pb(II) Sites of S. aureus pI258 CadC.
Busenlehner, L. S., Cosper, N. J., Scott, R. A., Rosen, B. P., Wong, M. D. & Giedroc, D. P. (2001)
Biochemistry 40, 4426-4436.
View:  PubMed

Conformational Heterogeneity in the C-Terminal Zinc Fingers of Human MTF-1: An NMR and Zinc Binding Study.
Giedroc, D. P., Chen, X., Pennella, M. A., & LiWang, A. (2001)
J. Biol. Chem. 276, 42322-42332.
View:  PubMed

Ratiometric Pulsed-Alkylation Mass Spectrometry of the Cysteine Pairs in Individual Zinc Fingers of MRE-Binding Transcription Factor-1 (MTF-1) as a Probe of Zinc Chelate Stability.
Apuy, J. L., Chen, X., Baldwin, T. O., Russell, D. H., & Giedroc, D. P. (2001)
Biochemistry 40, 15164-15175.
View:  PubMed

Metal-Response Element-Binding Transcription Factor-1 (MTF-1): Structure, Function and Regulation.
Giedroc, D. P., Chen, X., & Apuy, J. L.. (2001)
Antiox. Redox Signal. 3, 577-596 (invited review).
View:  PubMed

The Zinc Metalloregulatory Protein, Synechococcus PCC7942 SmtB, Binds a Single Zinc Ion per Monomer with High Affinity in a Tetrahedral Coordination Geometry.
VanZile, M. L., Cosper, N., Scott, R. A. & Giedroc, D. P. (2000)
Biochemistry 39, 11818-11829.
View:  PubMed

MRE-Binding Transcription Factor-1: Weak Zinc-Binding Finger Domains 5 and 6 Modulate the Structure, Affinity and Specificity of the Metal-Response Element Complex.
Chen, X., Chu, M., & Giedroc, D. P. (1999)
Biochemistry 38, 12915-12925.
View: PubMed

Structural and Functional Heterogeneity Among the Zinc-Fingers of Human MRE-Binding Transcription Factor-1 (MTF-1).
Chen, X., Agarwal, A., & Giedroc, D. P. (1998)
Biochemistry 37, 11152-11161.
View: PubMed

Reviews

2020-

Molecular evolution of transition metal bioavailability at the host-pathogen interface
Antelo, G. T., Vila, A. J., GIEDROC, D. P. and Capdevila, D. A. (2021)
Trends Microbiol. 29, 441-457 (doi: 10.1016/j.tim.2020.08.001.)
View: PubMed

H2S and reactive sulfur signaling at the host bacterial pathogen interface
Walsh, B. J. C. and GIEDROC, D. P. (2020)
J. Biol. Chem. 295, 13150-13168  (doi: 10.1074/jbc.REV120.011304)
View: PubMed

Iron acquisition by bacterial pathogens: Beyond tris-catecholate complexes
Zhang, Y., Sen, S., and GIEDROC, D. P. (2020)
ChemBioChem 21, 1955-1967 (doi: 10.1002/cbic.201900778)
View: PubMed

Multi-metal nutrient restriction at the host-microbial pathogen interface
Jordan, M. R., Wang, J., Capdevila, D. A., and GIEDROC, D. P. (2020)
Curr. Opin. Microbiol. 55, 17-25 (doi: 10.1016/j.mib.2020.01.010).
View: PubMed

Metal Ion Homeostasis
In Comprehensive Coordination Chemistry III (Li, Y., Que, L. eds.),
Wang, J., Capdevila, D. A., and GIEDROC, D. P. (2020)
Elsevier, Ltd., Oxford, UK (doi: 10.1016/B978-0-12-409547-2.14675-X).

Hydrogen sulfide signaling and enzymology
In Comprehensive Natural Products III: Chemistry and Biology, Vol 4, pp. 430–473 (Liu, H.-W., Begley, T., eds.)
Walsh, B. J. C., Brito, J. A., and GIEDROC, D. P. (2020)
Elsevier, Ltd., Oxford, UK
View: PubMed

2015-2019

A new player in bacterial sulfide-inducible transcriptional regulation
GIEDROC, D. P. (2017)
Mol. Microbiol. 105, 347-352 (doi: 10.1111/mmi.13726)
View: PubMed

Metallochaperones and metalloregulation in bacteria
Capdevila, D. A., Edmonds, K. A., & GIEDROC, D. P. (2017)
Essays Biochem. 61, 177-200 (doi: 10.1042/EBC20160076)
View: PubMed

Mammalian copper biology: Hitting the pause button in celebration of three pioneers and four decades of discovery (Commentary)
La Fontaine, S., Burke, R., & GIEDROC, D. P. (2016)
Metallomics 8, 810-812 (doi: 10.1039/c6mt90035f)
View: PubMed

Bacterial strategies to maintain zinc metallostasis at the host-pathogen interface
Capdevila, D. A., Wang, J. and GIEDROC, D. P. (2016)
J Biol Chem. 291, 20858-20868 (doi: 10.1074/jbc.R116.742023)
View: PubMed

Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial pathogen interface
Luebke, J. L., & GIEDROC, D. P. (2015)
Biochemistry 54, 3235-3249 (doi: 10.1021/acs.biochem.5b00085)
View: PubMed

2010-2014

Recent developments in copper and zinc homeostasis in bacterial pathogens
Braymer, J. J. & GIEDROC, D. P. (2014)
Curr. Opin. Chem. Biol. 19, 59-66 (doi: 10.1016/j.cbpa.2013.12.021)
View: PubMed

Copper transport and trafficking at the host-bacterial pathogen interface
Fu, Y., Chang, F.-M. J. & GIEDROC, D. P. (2014)
Acc Chem. Res. 47, 3605-3613 (doi: 10.1021/ar500300n)
View: PubMed

Insights into protein allostery in the CsoR/RcnR family of transcriptional repressors
Higgins, K. A. & GIEDROC, D. P.  (2014)
Chem. Lett. (Japan) 43, 20-25
View: PubMed

Manganese acquisition and homeostasis at the host-pathogen interface
Lisher, J. P. & GIEDROC, D. P. (2013)
Front Cell Infect Microbiol. 3 (doi: 10.3389/fcimb.2013.00091)
View: PubMed

Metal specificity of metallosensors
Higgins, K. A. & GIEDROC, D. P.  (2013)
In Metals in Cells (Culotta, V. & Scott, R. S., eds.), Chichester, UK. John Wiley & Sons, Ltd, pp. 209-224.
View: Online Publishing

Illuminating allostery in metal-sensing transcriptional regulators.
Grossoehme, N. E. & GIEDROC, D. P.  (2012)
Methods Mol. Biol. 875, 165-192.
View: PubMed

Allosteric coupling between transition metal-binding sites in homooligomeric metal sensor proteins.
Grossoehme, N. E. & GIEDROC, D. P.  (2012)
Methods Mol. Biol. 796, 31-51.
View: PubMed

Metal site occupancy and allosteric switching in bacterial metal sensor proteins.
Guerra, A. J., & GIEDROC, D. P.  (2012)
Arch. Biochem. Biophys. 519, 210-222.
View: PubMed

Metalloregulatory proteins: Metal selectivity and allosteric switching.
Reyes-Caballero, H., Campanello, G. C., & GIEDROC, D. P. (2011)
Biophys. Chem. 156, 103-114. (Invited Perspective)
View: PubMed

2009 and before

Hydrogen peroxide sensing in Bacillus subtilis: it is all about the (metallo)regulator.
GIEDROC, D. P. (2009)
Mol. Micro. 73, 1-4 (Invited commentary)
View: PubMed

Coordination chemistry of bacterial metal transport and sensing.
Ma, Z, Jacobsen, F. E., & GIEDROC, D. P.  (2009)
Chem. Rev.109, 4644-4681.
View: PubMed

Metal Sensor Proteins: Nature’s metalloregulated allosteric switches.
Giedroc, D. P. and Arunkumar, A. I. (2007)
Dalton Trans., 3107-3120 (Invited Perspective).
View:  PubMed

Structural Determinants of Metal Selectivity in Prokaryotic Metal-Responsive Transcriptional Regulators.
Pennella, M. A., & Giedroc, D. P. (2005)
Biometals 18, 413-428 (invited review).
View:  PubMed

The SmtB/ArsR Family of Metalloregulatory Transcriptional Repressors: Structural Insights into Prokaryotic Metal Resistance.
Busenlehner, L. S., Pennella, M. A., & Giedroc, D. P. (2003)
FEMS Microbiol. Rev. 27, 131-144 (invited review).
View:  PubMed