Department of Physiology JHU School of Medicine
Publications by the Svetlana Lutsenko Laboratory

Peer Reviewed Original Science Publications

Wilmarth PA, Short KK, Fiehn O, Lutsenko S, David LL, Burkhead JL. (2012) A systems
approach implicates nuclear receptor targeting in the Atp7b(-/-) mouse model of
Wilson's disease Metallomics 4(7):660-8

Otoikhian AA, Barry AN, Mayfield M, Nilges MJ, Huang Y, Lutsenko S, Blackburn NJ. (2012)
The Lumenal Loop M672-P707 of the Menkes Protein (ATP7A) Transfers Copper to Peptidylglycine
Monooxygenase. J Am Chem Soc 134(25):10458-68

Gray LW, Peng F, Molloy SA, Pendyala VS, Muchenditsi A, Muzik O, Lee J, Kaplan JH, Lutsenko S (2012)
Urinary Copper Elevation in a Mouse Model of Wilson's Disease is a Regulated Process to Specifically
Decrease the Hepatic Copper Load PloS One 7(6):e38327

Schushan M, Bhattacherjee, A., Ben-Tal N, Lutsenko S (2012) A Structural Model of the Copper
ATPase ATP7B to Facilitate Analysis of Wilson disease-causing Mutations and Studies of
the Transport Mechanism Metallomics 4(7):669-78

Hatori Y, Clasen S, Hasan NM, Barry AN, Lutsenko S. (2012) Functional partnership of the copper export
machinery and glutathione balance in human cells. J Biol Chem. 287(32):26678-87

Hasan NM, Gupta A, Polishchuk E, Yu CH, Polishchuk R, Dmitriev OY, Lutsenko S. (2012) Molecular Events
Initiating Exit of a Copper-transporting ATPase ATP7B From the Trans-Golgi Network. J Biol Chem 287(43):36041-50

Hasan NM, Lutsenko S. (2012) Regulation of copper transporters in human cells. Curr Top Membr. 69:137-61

Hirayama T, Van de Bittner GC, Gray LW, Lutsenko S, Chang JC (2012) A near-infrared
fluorescent sensor for in vivo copper imaging in a Wilson's disease model
Proc Natl Acad Sci USA 109(7):2228-33

Huster D, Kühne A, Bhattacharjee A, Raines L, Jantsch V, Noe J, Schirrmeister W, Sommerer I,
Sabri O, Berr F, Mossner J, Stieger B, Caca K, Lutsenko S (2012) Diverse Functional
Properties of Wilson Disease ATP7B Variants Gastroenterology 142(4):947-956

Roybal JL, Endo M, Radu A, Gray L, Todorow CA, Zoltick PW, Lutsenko S, Flake AW (2012)
Early gestational gene transfer with targeted ATP7B expression in the liver improves
phenotype in a murine model of Wilson's disease. Gene Ther. (in pres)

Peng F, Lutsenko S, Sun X, Muzik O.(2011) Imaging Copper Metabolism Imbalance
in Atp7b (-/-) Knockout Mouse Model of Wilson's Disease with PET-CT and Orally
Administered 64CuCl2 Mol Imaging Biol.(in press)

Barry AN, Otoikhian A, Bhatt S, Shinde U, Tsivkovskii R, Blackburn NJ, Lutsenko S. (2011)
The lumenal loop Met672-Pro707 of copper-transporting ATPase ATP7A binds metals and facilitates
copper release from the intramembrane sites. J Biol Chem. 286(30):26585-94

Dmitriev OY, Bhattacharjee A, Nokhrin S, Uhlemann EE, and Lutsenko S (2011)
“Difference In Stability of the N-Domain Underlies Distinct Intracellular Properties
of the E1064A and H1069Q Mutants of Cu-transporting ATPase ATP7B” J. Biol. Chem 286(18):16355-62

Gupta A, Bhattacharjee A, Braiterman L., Hubbard AL, Dmitriev OY, Lutsenko S (2011)
“Cellular Copper Levels Determine the Phenotype of the Arg875 Variant of Cu-Transporting
ATPase ATP7B” Proc Natl Acad Sci U S A, 108(13):5390-5

Peng F, Lutsenko S, Sun X, Muzik O (2012) Positron Emission Tomography of Copper
Metabolism in the Atp7b (-/-) Knock-out Mouse Model of Wilson's Disease. Mol Imaging Biol 14(1):70-8.

Burkhead JL, Ralle M, Wilmarth P, David L, and Lutsenko S (2011)“Elevated Copper
Induces Selective Remodeling of RNA Splicing Machinery in the Mouse Model of
Wilson’s disease” J. Mol.Biol 406(1):44-58

Ralle M, Huster D, Vogt S, Schirrmeister W, Burkhead JL, Capps TR, Gray L, Lai B,
Maryon E, Lutsenko S. (2010) Wilson's disease at a single cell level: intracellular copper
trafficking activates compartment-specific responses in hepatocytes J Biol Chem. 285(40):30875-83.

LeShane ES, Shinde U, Walker JM, Barry AN, Blackburn NJ, Ralle M, Lutsenko S (2009)
Interactions between Copper-binding Sites Determine the Redox Status and Conformation of
the Regulatory N-terminal Domain of ATP7B J. Biol. Chem, 285(9):6327-36

Bartee MY, Ralle M, and Lutsenko S (2009) “The Loop Connecting Metal-Binding Domains 3
And 4 of ATP7B Is A Target of A Kinase Mediated Phosphorylation” Biochemistry 48(24):5573-81

Wright LM, Huster D, Lutsenko S, Wrba F, Ferenci P, Fimmell C. (2009) “Hepatocytes GP73
expression in Wilson’s disease”. J. Hepatology 51(3):557-64

Mangala LS, Zuzel V, Schmandt R, Halder JB, Armaiz-Pena GN, Spannuth WA, Lin YG, Kim SW,
Kim TJ, Shahzad MMK, Lee JW, Hwang JY, Nick AM, Vivas- Mejia PE, Wolf J, Coleman RL, Siddik ZH,
Lopez-Berestein G, Lutsenko S, Sood AK (2009) “Therapeutic Targeting of ATP7B: Reversing
Cisplatin Resistance in Ovarian Carcinoma” Clinical Cancer Research 15:3770-80

Barnes NL, Bartee MY, Braiterman L., Gupta A., Ustiyan V, Zuzel V., Kaplan JH, Hubbard A.,
and Lutsenko S (2008) “Cell Specific Trafficking Suggests a New Role for Renal ATP7B In
the Intracellular Copper Storage” Traffic 10(6):767-79

Ralle M, Lutsenko S. (2009) Quantitative imaging of metals in tissues. Biometals. 22(1):197-205.

Leonhardt K, Gebhardt R, Mossner J, Lutsenko S (senior co-author), Huster D. (2009) Functional
interactions of Cu-ATPase ATP7B with cisplatin and the role of ATP7B in cells resistance
to the drug. J Biol Chem. 284(12):7793-802

Dolgova NV, Olson D, Lutsenko S, Dmitriev OY. (2009) The soluble metal-binding domain of
copper transporter ATP7B binds and detoxifies cisplatin. Biochem J. 419(1):51-6

Burkhead JL, Morgan CT, Shinde U, Haddock G, Lutsenko S (2009) Domain Organization of
COOMD1 and Targeting to the Membrane via Specific Interactions with PtdIns(4,5)P2
J Biol. Chem, 284(1):696-707

Braiterman L, Nyasae L, Bustos R, Guo Y, Lutsenko S, and Hubbard AL (2008) Apical targeting
and Golgi retention signals reside within a 9-amino acid sequence in the copper-ATPase, ATP7B.
Am J Physiol Gastrointest Liver Physiol. 296(2):G433-44.

Lörinczi E, Tsivkovskii R, Haase W, Bamberg E, Lutsenko S (senior co-author), Friedrich T. (2008)
Delivery of the Cu-transporting ATPase ATP7B to the plasma membrane in Xenopus oocytes.
Biochim. Biophys Acta. 1778(4):896-906

Linz R., Barnes NL, Zimnicka AM, Kaplan JH, Eipper B, and Lutsenko S (2007)
The Intracellular Targeting of Copper-transporting ATPase ATP7A in a normal and ATP7b-/- Kidney.
Am. J. Physiol (Renal Physiology) 294(1):F53-61

Huster D, Purnat TD, Ralle M, Fiehn O, Stuckert F, Burkhead JL, Olson NE, Teupser D, Lutsenko S (2007)
High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model
of Wilson disease J Biol Chem 282: 8343-55

Dmitriev OY, Tsivkovskii R, Abildgaard F, Lutsenko S. (2006) NMR assignment of the Wilson disease
associated protein N-domain. J Biomol NMR 36 Suppl 5:61

Dmitriev O, Tsivkovskii R, Abildgaard F, Morgan CT, Markley JL, and Lutsenko S (2006) Solution
Structure of the N-domain of Wilson disease Protein: Unique Nucleotide-binding Environment and
Effects of Disease Mutations Proc. Natl. Acad. Sci. USA, 103(14):5302-7

Huster D, Finegold MJ, Vanderwerf SM, Morgan CT, Nixon R, Gilliam TC, and Lutsenko S. (2006)
Consequences of Copper Accumulation in the Livers of the Wilson Disease Gene Knock-Out Mice
Am.J Pathology, 168(2):423-34

Barnes NL, Tsivkovskii R, Tsivkovskaya N, Lutsenko S. (2005) The Copper-Transporting ATPases,
Menkes and Wilson Disease Proteins, have Distinct Roles in Adult and Developing Cerebellum
J Biol Chem 280:9640-5.

Morgan CT, Tsivkovskii R, Kosinsky YA, Efremov RG, Lutsenko S. (2004) Distinct functional
properties of the nucleotide-binding domain of ATP7B, the human copper-transporting ATPase:
analysis of the Wilson disease mutations E1064A, H1069Q, R1151H, and C1104F.
J Biol Chem. 279:36363-71.

Efremov RG, Kosinsky YA, Nolde DE, Tsivkovskii R, Arseniev AS, Lutsenko S. (2004) Molecular
modeling of the nucleotide-binding domain of Wilson's disease protein: location of the ATP-binding
site, domain dynamics and potential effects of the major disease mutations.
Biochem J. 382(Pt 1):293-305.

Ralle M., Lutsenko S., Blackburn N.J. (2004) Copper Transfer to the N-terminal Domain of the
Wilson Disease Protein (ATP7B). X-ray Absorption Spectroscopy of Reconstituted and Chaperone-Loaded
Metal Binding Domains and Their Interaction with Exogenous Ligands. J. Inorg Biochem. 98:765-74.

Walker JM, Huster D, Ralle M, Morgan CT, Blackburn NJ, Lutsenko S. (2004) The N-terminal metal-binding
site 2 of the Wilson’s disease protein plays a key role in the transfer of copper from Atox1.
J Biol Chem. 279:15376-84

Huster D. and Lutsenko S. (2003) The Distinct Roles of the N-terminal Copper-binding Sites in Regulation
of Catalytic Activity of the Wilson’s disease protein J.Biol.Chem. 278:32212-8

Ralle M., Lutsenko S., Blackburn N.J (2003) X-ray absorption spectroscopy of the copper chaperone
HAH1 reveals a linear 2-coordinate Cu(I) center capable of adduct formation with exogenous
thiols and phosphines. J Biol Chem. 278:23163-70

Tsivkovskii R., Efremov R.G., Lutsenko S. (2003) The Role of the Invariant His1069 in Folding and
Function of Wilson’s disease Protein, the Human Copper-transporting ATPase ATP7B
J. Biol. Chem. 278:13302-8.

Gerbasi V., Lutsenko S., and Lewis E.J. (2003) A Mutation in the ATP7B Copper Transporter Causes
Reduced Dopamine ß-Hydroxylase and Norepinephrine in Mouse
Adrenal Neurochemical Research 28:867-73

Huster, D., Hoppert, M., Zinke, J., Lutsenko, S., Lehmann, C., Mossner, J., Berr, F., and Caca, K. (2003)
Defective cellular localization of mutant ATP7B in Wilson’s disease patients and hepatoma cell lines.
Gastroenterology, 124:335-45

Vanderwerf, S.M., and Lutsenko, S. (2002) The Wilson's disease protein expressed in Sf9 cells is phosphorylated.
Biochem Soc Trans. 30(4):739-41.

Walker, J.M., Tsivkovskii, R., and Lutsenko, S. (2002) Metallochaperone Atox1 Transfers Copper to the
NH2-terminal Domain of the Wilson's Disease Protein and Regulates Its Catalytic Activity.
J Biol Chem. 277(31):27953-9.

Tsivkovskii R., Eisses J.F., Kaplan J.H., and Lutsenko S. (2002) Functional Properties of the
Copper-transporting ATPase ATP7B (the Wilson’s disease protein) expressed in insect cells.
J. Biol. Chem. 277: 976-983.

Vanderwerf, S.M., Cooper, M.J., Stetsenko, I.V., and Lutsenko, S. (2001) Copper Specifically
Regulates Intracellular Phosphorylation of the Wilson's Disease Protein, a Human Copper-Transporting ATPase.
J. Biol. Chem. 276: 36289-94.

Tsivikovskii, R., MacArthur B.C., and Lutsenko, S. (2001) The K1010-K1325 Fragment of the Wilson’s
Disease Protein Binds Nucleotides And Interacts With the N-Terminal Domain of This Protein In a
Copper-Dependent Manner. J. Biol. Chem. 276(3):2234-42.

Noll, M., and Lutsenko, S. (2000) Expression of ZntA, A Zinc-Transporting P1-type ATPase, Is
Specifically Regulated By Zinc And Cadmium IUBMB Life 49(4):297-302.

Gatto, C., Lutsenko, S., Shin, J.M., Sachs, G., and Kaplan, J.H. (1999) Stabilization of the
H+,K+-ATPase M5M6 hairpin by K+ ions. Mechanistic significance for P2-type ATPases.
J. Biol. Chem. 274:13737-13740.

Buiakova, O.I., Xu, J., Lutsenko, S., Zeitlin, S., Das, K., Das, Sh., Ross, B.M., Mekios, C.,
Scheinberg, H., and Gilliam, T.C. (1999) Null mutation of the murine ATP7B (Wilson disease)
gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.
Hum. Mol. Genet. 8(9):1665-1671.

Xia, X.M., Fakler, B., Rivard, A., Wayman, G., Johnson-Pais, T., Keen, J.E., Ishii, T., Hirschberg, B.,
Bond, C.T., Lutsenko, S., Maylie, J., and Adelman, J.P. (1998) Mechanism of calcium gating in small
conductance calcium-activated potassium channels. Nature 395:503-507.

Ralle, M., Cooper, M.J., Lutsenko, S., and Blackburn, N.J. (1998) X-Ray Absorption Studies On The
Soluble N-Terminal Domain Of The Menkes Disease Protein (N-MNK-P) With Multiple Copper Site Occupancy.
Evidence For A Two-Coordinate Copper-Cysteinate Coordination Environment.
J. Am. Chem. Soc. 120:13525-13526.

Noll, M., Petrukhin, K., and Lutsenko, S. (1998) Identification Of A Novel Transcription Regulator
From Proteus Mirabilis, PMTR, Revealed The Possible Role Of The YJAI Protein In Balancing Zinc In E. Coli.
J. Biol. Chem. 273:21393-21401.

Invited review articles:

Burkhead JL, Gray LW, Lutsenko S. (2011) Systems biology approach to Wilson's disease.
Biometals, 24(3):455-66

Lutsenko S., Bhattacharjee A., Hubbard AL (2010) Copper handling machinery of the brain
Metallomics 2(9):596-608

Lutsenko S (2010) “Human Copper Homeostasis: A Network of Interconnected Pathways”
Curr. Opin.Chem.Biol. 14(2):211-7

Barry AN, Shinde U, and Lutsenko S (2010) “Structural Organization of Human Cu-ATPases:Learning
From Building Blocks” J Biol Inorg Chem 15(1):47-59

Gupta A and Lutsenko S. (2009) “Human Copper Transporters: Mechanism, the Role in Human Diseases,
and Therapeutic Potential” Future Medicinal Chemistry 1(6):1125-1142

Kaplan JH and Lutsenko S (2009) “Copper Transport in Mammalian Cells: Special Care for a Metal
with Special Needs” J. Biol. Chem.(mini-review) 284(38):25461-5

Lutsenko S (2008) “Atp7b-/- Mice as a Model for Studies of Wilson’s disease”
Biochem Soc.Trans 36(Pt 6):1233-8

Lutsenko S, Gupta A, Burkhead JL, and Zuzel V (2008) “Cellular Multitasking: The Dual Role
of Human Cu-ATPases in Cofactor Delivery and Intracellular Copper Balance”
Archives of Biochem Biophys (special issue) 476(1): 22-32

Linz R and Lutsenko S “Copper-transporting ATPases ATP7A and ATP7B: cousins, not twins” (2007)
J. Bioenerg Biomemranes (miniseries) 39(5-6):403-7

Huster D and Lutsenko S (2007) Wilson disease: not just a copper disorder.
Analysis of a Wilson disease model reveals the link between copper and lipid metabolism
Molecular Biosystems 3(12):816-24 (highlight article with cover image)

Lutsenko S, LeShane ES, Shinde U (2007) Biochemical basis of regulation of human
copper-transporting ATPases Arch Biochem Biophys 463(2):134-48

Bartee MY and Lutsenko S (2007) Hepatic copper-transporting ATPase ATP7B: function and
inactivation at the molecular and cellular level. Biometals 20(3-4) 627-37

Lutsenko S, Barnes NL, Bartee MY, Dmitriev O (2007) Function and Regulation of Human
Copper-transporting ATPases Physiological Reviews, 87(3):1011-46

Lutsenko, S., and Petris, M. (2002) Function and Regulation of the Mammalian
Copper-transporting ATPases: Insights from Biochemical and Cell Biological Approaches.
J. Memb. Biology 191(1):1-12

Lutsenko, S., Efremov, R.G., Tsivkovskii, R., and Walker, J.M. (2002) Human Copper-Transporting
ATPase ATP7B (The Wilson’s Disease Protein): Biochemical Properties And Regulation.
J. Biomemb. Bioenerg. 34, 351-362

Lutsenko, S., and Kaplan, J.H. (1995) Organization of P-type ATPases: significance of
structural diversity. Biochemistry 34:15607-15613.

Book Chapters:

Hatori Y. and Lutsenko S. (2010) Chapter for the Second Edition of the
“Encyclopedia of Biological Chemistry" in press

Barry AN, Akram Z, and Lutsenko S (2010) “Mechanism of Human Copper Transporter Wilson disease
protein” , chapter for “Protein Folding and Disease” in press

Lutsenko S., Tsivkovskii R., Walker J.M. (2002) Functional Properties of the Human Copper-Transporting
ATPase ATP7B (the Wilson’s disease Protein) and regulation by Metallochaperone Atox1 in “Na,K-ATPase
and Related Cation Pumps: Structure, Function, and Regulatory Mechanisms”, Volume 986 of
the Annals of the New York Academy of Sciences, edited by Peter Leth Jørgensen,
Steven J.D. Karlish, and Arvid B. Maunsbach

Tsivkovskii R, Purnat T, Lutsenko S. (2003) “Copper-transporting ATPases: the key
regulators of intracellular copper concentrations” Handbook of ATPases (Eds, Futai, Kaplan, Wada)
Wiley-VCH Verlag GmbH, Weinheim, chapter 5.

Lutsenko, S., Tsivkovskii, R., Cooper, M.J., MacArthur, B.C., and Bachinger H-P. (2002)
Biochemistry of the Wilson’s Disease Protein. Chapter in Handbook of Copper Pharmacology and
Toxicology (ed. E.J. Massaro) Humana Press, Totowa, NJ. pp.35-51.

Lutsenko, S., and Kaplan, J.H. (1994) Rearrangements of the membrane-associated segments
of Na+,K+-ATPase upon phosphorylation, ion-occlusion and ouabain binding. In: The sodium
pump: structure, mechanism, hormonal control and its role in disease
(ed. E.Bamberg and W.Schoner) Darmstadt: Steinkopff; New York: Springer, pp.413-416.

Kaplan, J.H., Arguello, J.M., Ellis-Davies, G.C.R., and Lutsenko S. (1994)
The stabilization of Cation Binding and its Relation to Na+,K+-ATPase Structure and Function.
In The Na-pump: structure, mechanism, hormonal control and its role in disease (ed. E.Bumberg and W.Schoner)
Darmstadt:Steinkopff; New York: Springer, pp.321-329.

Modyanov, N., Lutsenko, S., Chertova, E., and Efremov, R. (1991) Architecture of the sodium pump
molecule: probing the folding of the hydrophobic domain. In The Sodium Pump: Structure, Mechanism,
and Regulation (ed. J.H. Kaplan and P. De Weer), pp. 99-117

Lutsenko Lab
Department of Physiology
Johns Hopkins University
725 N. Wolfe Street
203 Hunterian
Baltimore, MD 21205
(410) 614-4661 (tel)
(410) 955-0461 (fax)