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Article ; Online: Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.

Ketkar, Amit / Sewilam, Reham S / McCrury, Mason J / Hall, Jaycelyn S / Bell, Ashtyn / Paxton, Bethany C / Tripathi, Shreyam / Gunderson, Julie E C / Eoff, Robert L

RSC chemical biology

2023 Volume 4, Issue 7, Page(s) 466–485

Abstract: In some organisms, the replication of G-quadruplex (G4) structures is supported by the Rev1 DNA polymerase. We previously showed that residues in the insert-2 motif of human Rev1 (hRev1) increased the affinity of the enzyme for G4 DNA and mediated ... ...

Abstract	In some organisms, the replication of G-quadruplex (G4) structures is supported by the Rev1 DNA polymerase. We previously showed that residues in the insert-2 motif of human Rev1 (hRev1) increased the affinity of the enzyme for G4 DNA and mediated suppression of mutagenic replication near G4 motifs. We have now investigated the conservation of G4-selective properties in Rev1 from other species. We compared Rev1 from
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article
ISSN	2633-0679
ISSN (online)	2633-0679
DOI	10.1039/d3cb00027c
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Article ; Online: Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells.

Reed, Megan R / Maddukuri, Leena / Ketkar, Amit / Byrum, Stephanie D / Zafar, Maroof K / Bostian, April C L / Tackett, Alan J / Eoff, Robert L

NAR cancer

2021 Volume 3, Issue 2, Page(s) zcab014

Abstract: Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis- ... ...

Abstract	Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis-chloroethylnitrosourea (BCNU). Activation of the Chk1 arm of the replication stress response (RSR) was reduced when TDO activity was blocked prior to BCNU treatment, whereas phosphorylation of serine 33 (pS33) on replication protein A (RPA) was enhanced-indicative of increased fork collapse. Analysis of quantitative proteomic results revealed that TDO inhibition reduced nuclear 53BP1 and sirtuin levels. We confirmed that cells lacking TDO activity exhibited elevated gamma-H2AX signal and defective recruitment of 53BP1 to chromatin following BCNU treatment, which corresponded with delayed repair of DNA breaks. Addition of exogenous KYN increased the rate of break repair. TDO inhibition diminished SIRT7 deacetylase recruitment to chromatin, which increased histone H3K18 acetylation-a key mark involved in preventing 53BP1 recruitment to sites of DNA damage. TDO inhibition also sensitized cells to ionizing radiation (IR)-induced damage, but this effect did not involve altered 53BP1 recruitment. These experiments support a model where TDO-mediated KYN signaling helps fuel a robust response to replication stress and DNA damage.
Language	English
Publishing date	2021-04-09
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcab014
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Article ; Online: Residues in the RecQ C-terminal Domain of the Human Werner Syndrome Helicase Are Involved in Unwinding G-quadruplex DNA.

Ketkar, Amit / Voehler, Markus / Mukiza, Tresor / Eoff, Robert L

The Journal of biological chemistry

2017 Volume 292, Issue 8, Page(s) 3154–3163

Abstract: The structural and biophysical properties typically associated with G-quadruplex (G4) structures render them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ family ... ...

Abstract	The structural and biophysical properties typically associated with G-quadruplex (G4) structures render them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ family helicase that has been implicated in the efficient processing of G4 DNA structures. The aim of this study was to identify the residues of WRN involved in the binding and ATPase-driven unwinding of G4 DNA. Using a c-Myc G4 DNA model sequence and recombinant WRN, we have determined that the RecQ-C-terminal (RQC) domain of WRN imparts a 2-fold preference for binding to G4 DNA relative to non-G4 DNA substrates. NMR studies identified residues involved specifically in interactions with G4 DNA. Three of the amino acids in the WRN RQC domain that exhibited the largest G4-specific changes in NMR signal were then mutated alone or in combination. Mutating individual residues implicated in G4 binding had a modest effect on WRN binding to DNA, decreasing the preference for G4 substrates by ∼25%. Mutating two G4-interacting residues (T1024G and T1086G) abrogated preferential binding of WRN to G4 DNA. Very modest decreases in G4 DNA-stimulated ATPase activity were observed for the mutant enzymes. Most strikingly, G4 unwinding by WRN was inhibited ∼50% for all three point mutants and >90% for the WRN double mutant (T1024G/T1086G) relative to normal B-form dsDNA substrates. Our work has helped to identify residues in the WRN RQC domain that are involved specifically in the interaction with G4 DNA.
MeSH term(s)	DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Repair ; DNA Replication ; G-Quadruplexes ; Humans ; Models, Molecular ; Mutation ; Protein Domains ; Werner Syndrome/enzymology ; Werner Syndrome/genetics ; Werner Syndrome/metabolism ; Werner Syndrome Helicase/chemistry ; Werner Syndrome Helicase/genetics ; Werner Syndrome Helicase/metabolism
Chemical Substances	DNA (9007-49-2) ; Werner Syndrome Helicase (EC 3.6.4.12)
Language	English
Publishing date	2017-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M116.767699
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Article ; Online: Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs.

Ketkar, Amit / Smith, Lane / Johnson, Callie / Richey, Alyssa / Berry, Makayla / Hartman, Jessica H / Maddukuri, Leena / Reed, Megan R / Gunderson, Julie E C / Leung, Justin W C / Eoff, Robert L

Nucleic acids research

2021 Volume 49, Issue 4, Page(s) 2065–2084

Abstract: We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for ... ...

Abstract	We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.
MeSH term(s)	Cell Line ; DNA/chemistry ; DNA/metabolism ; DNA Replication ; DNA-Directed DNA Polymerase/metabolism ; G-Quadruplexes ; Genes, myc ; Humans ; Models, Molecular ; Mutation ; Nucleotide Motifs ; Nucleotidyltransferases/chemistry ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Protein Binding
Chemical Substances	DNA (9007-49-2) ; Nucleotidyltransferases (EC 2.7.7.-) ; REV1 protein, human (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2021-02-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab041
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Article ; Online: Inhibition of Human DNA Polymerases Eta and Kappa by Indole-Derived Molecules Occurs through Distinct Mechanisms.

Ketkar, Amit / Maddukuri, Leena / Penthala, Narsimha R / Reed, Megan R / Zafar, Maroof K / Crooks, Peter A / Eoff, Robert L

ACS chemical biology

2019 Volume 14, Issue 6, Page(s) 1337–1351

Abstract: Overexpression of human DNA polymerase kappa (hpol κ) in glioblastoma is associated with shorter survival time and resistance to the alkylating agent temozolomide (TMZ), making it an attractive target for the development of small-molecule inhibitors. We ... ...

Abstract	Overexpression of human DNA polymerase kappa (hpol κ) in glioblastoma is associated with shorter survival time and resistance to the alkylating agent temozolomide (TMZ), making it an attractive target for the development of small-molecule inhibitors. We previously reported on the development and characterization of indole barbituric acid-derived (IBA) inhibitors of translesion DNA synthesis polymerases (TLS pols). We have now identified a potent and selective inhibitor of hpol κ based on the indole-aminoguanidine (IAG) chemical scaffold. The most promising IAG analogue, IAG-10, exhibited greater inhibitory action against hpol κ than any other human Y-family member, as well as pols from the A-, B-, and X-families. Inhibition of hpol κ by IAG analogues appears to proceed through a mechanism that is distinct from inhibition of hpol η based on changes in DNA binding affinity and nucleotide insertion kinetics. By way of comparison, both IAG and IBA analogues inhibited binary complex formation by hpol κ and ternary complex formation by hpol η. Decreasing the concentration of enzyme and DNA in the reaction mixture lowered the IC
MeSH term(s)	Alkylation ; DNA Damage ; DNA-Directed DNA Polymerase/drug effects ; Enzyme Inhibitors/pharmacology ; Humans ; Indoles/pharmacology ; Inhibitory Concentration 50
Chemical Substances	Enzyme Inhibitors ; Indoles ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; POLK protein, human (EC 2.7.7.7) ; Rad30 protein (EC 2.7.7.7)
Language	English
Publishing date	2019-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.9b00304
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Article ; Online: Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-M

Christov, Plamen P / Richie-Jannetta, Robyn / Kingsley, Philip J / Vemulapalli, Anoop / Kim, Kwangho / Sulikowski, Gary A / Rizzo, Carmelo J / Ketkar, Amit / Eoff, Robert L / Rouzer, Carol A / Marnett, Lawrence J

Chemical research in toxicology

2021 Volume 34, Issue 12, Page(s) 2567–2578

Abstract: The lipid peroxidation product malondialdehyde and the DNA peroxidation product base-propenal react with dG to generate the exocyclic adduct, ... ...

Abstract	The lipid peroxidation product malondialdehyde and the DNA peroxidation product base-propenal react with dG to generate the exocyclic adduct, M
MeSH term(s)	Chromatography, Liquid ; DNA-Directed DNA Polymerase/metabolism ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/chemistry ; Deoxyguanosine/metabolism ; Humans ; Molecular Structure ; Oligonucleotides/chemical synthesis ; Oligonucleotides/chemistry ; Oligonucleotides/metabolism ; Tandem Mass Spectrometry ; DNA Polymerase iota
Chemical Substances	Oligonucleotides ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Deoxyguanosine (G9481N71RO) ; DNA Polymerase iota (EC 2.7.7.7) ; POLI protein, human (EC 2.7.7.7)
Language	English
Publishing date	2021-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.1c00334
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Zs.A 2320: Show issues

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Article: Human Translesion Polymerase Îº Exhibits Enhanced Activity and Reduced Fidelity Two Nucleotides from G-Quadruplex DNA

Eddy, Sarah / Tillman Magdalena / Maddukuri Leena / Ketkar Amit / Zafar Maroof K / Eoff Robert L

Biochemistry. 2016 Sept. 20, v. 55, no. 37

2016

Abstract: We have investigated the in vitro properties of human Y-family polymerase Îº (hpol Îº) on G-quadruplex DNA (G4 DNA). Similar to hpol Î·, another Y-family member implicated in replication of G4 motifs, hpol Îº bound G4 DNA with a 5.7-fold preference over ... ...

Abstract	We have investigated the in vitro properties of human Y-family polymerase Îº (hpol Îº) on G-quadruplex DNA (G4 DNA). Similar to hpol Î·, another Y-family member implicated in replication of G4 motifs, hpol Îº bound G4 DNA with a 5.7-fold preference over control, non-G4 DNA. Results from pol extension assays are consistent with the notion that G-quadruplexes present a stronger barrier to DNA synthesis by hpol Îº than they do to that by hpol Î·. However, kinetic analysis revealed that hpol Îº activity increases considerably when the enzyme is 2â3 nucleotides from the G4 motif, a trend that was reported previously for hpol Î·, though the increase was less pronounced. The increase in hpol Îº activity on G4 DNA was readily observed in the presence of either potassium or sodium but much less so when lithium was used in the buffer. The increased activity 2â3 nucleotides from the G4 motif was accompanied by a decrease in the fidelity of hpol Îº when the counterion was either potassium or sodium but not in the presence of lithium. The activity of hpol Îº decreased progressively as the primer was moved closer than 2 nucleotides from the G4 motif when either potassium or sodium was used to stabilize the G-quadruplex. Interestingly, the decrease in catalytic activity at the site of the quadruplex observed in potassium-containing buffer was accompanied by an increase in fidelity on G4 substrates versus control non-G4 substrates. This trend of increased fidelity in copying a tetrad-associated guanine was observed previously for hpol Î·, but not for the B-family member hpol Îµ, which exhibited a large decrease in both efficiency and fidelity in the attempt to copy the first guanine in the G4 motif. In summary, hpol Îº activity was enhanced relative to those of other Y-family members when the enzyme is 2â3 nucleotides from the G4 motif, but hpol Îº appears to be less competent than hpol Î· at copying tetrad-associated guanines.
Keywords	DNA ; catalytic activity ; guanine ; humans ; kinetics ; lithium ; nucleotides ; potassium ; sodium
Language	English
Dates of publication	2016-0920
Size	p. 5218-5229.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021%2Facs.biochem.6b00374
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Article ; Online: Human Translesion Polymerase κ Exhibits Enhanced Activity and Reduced Fidelity Two Nucleotides from G-Quadruplex DNA.

Eddy, Sarah / Tillman, Magdalena / Maddukuri, Leena / Ketkar, Amit / Zafar, Maroof K / Eoff, Robert L

Biochemistry

2016 Volume 55, Issue 37, Page(s) 5218–5229

Abstract: We have investigated the in vitro properties of human Y-family polymerase κ (hpol κ) on G-quadruplex DNA (G4 DNA). Similar to hpol η, another Y-family member implicated in replication of G4 motifs, hpol κ bound G4 DNA with a 5.7-fold preference over ... ...

Abstract	We have investigated the in vitro properties of human Y-family polymerase κ (hpol κ) on G-quadruplex DNA (G4 DNA). Similar to hpol η, another Y-family member implicated in replication of G4 motifs, hpol κ bound G4 DNA with a 5.7-fold preference over control, non-G4 DNA. Results from pol extension assays are consistent with the notion that G-quadruplexes present a stronger barrier to DNA synthesis by hpol κ than they do to that by hpol η. However, kinetic analysis revealed that hpol κ activity increases considerably when the enzyme is 2-3 nucleotides from the G4 motif, a trend that was reported previously for hpol η, though the increase was less pronounced. The increase in hpol κ activity on G4 DNA was readily observed in the presence of either potassium or sodium but much less so when lithium was used in the buffer. The increased activity 2-3 nucleotides from the G4 motif was accompanied by a decrease in the fidelity of hpol κ when the counterion was either potassium or sodium but not in the presence of lithium. The activity of hpol κ decreased progressively as the primer was moved closer than 2 nucleotides from the G4 motif when either potassium or sodium was used to stabilize the G-quadruplex. Interestingly, the decrease in catalytic activity at the site of the quadruplex observed in potassium-containing buffer was accompanied by an increase in fidelity on G4 substrates versus control non-G4 substrates. This trend of increased fidelity in copying a tetrad-associated guanine was observed previously for hpol η, but not for the B-family member hpol ε, which exhibited a large decrease in both efficiency and fidelity in the attempt to copy the first guanine in the G4 motif. In summary, hpol κ activity was enhanced relative to those of other Y-family members when the enzyme is 2-3 nucleotides from the G4 motif, but hpol κ appears to be less competent than hpol η at copying tetrad-associated guanines.
MeSH term(s)	DNA/metabolism ; DNA Damage ; DNA-Directed DNA Polymerase/metabolism ; Fluorescence Polarization ; G-Quadruplexes ; Humans ; Kinetics
Chemical Substances	DNA (9007-49-2) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; POLK protein, human (EC 2.7.7.7)
Language	English
Publishing date	2016-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.6b00374
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Article ; Online: A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells.

Zafar, Maroof K / Maddukuri, Leena / Ketkar, Amit / Penthala, Narsimha R / Reed, Megan R / Eddy, Sarah / Crooks, Peter A / Eoff, Robert L

Biochemistry

2018 Volume 57, Issue 7, Page(s) 1262–1273

Abstract: Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric ... ...

Abstract	Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cisplatin/pharmacology ; DNA-Directed DNA Polymerase/metabolism ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; Indoles/chemistry ; Indoles/pharmacology ; Molecular Docking Simulation ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Thiobarbiturates/chemistry ; Thiobarbiturates/pharmacology
Chemical Substances	Antineoplastic Agents ; Enzyme Inhibitors ; Indoles ; Pyrimidines ; Small Molecule Libraries ; Thiobarbiturates ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Rad30 protein (EC 2.7.7.7) ; thiobarbituric acid (M1YZW5SS7C) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2018-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/acs.biochem.7b01176
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Article: Kinetic Analysis of Human PrimPol DNA Polymerase Activity Reveals a Generally Error-Prone Enzyme Capable of Accurately Bypassing 7,8-Dihydro-8-oxo-2â²-deoxyguanosine

Zafar, Maroof K / Ketkar Amit / Lodeiro Maria F / Cameron Craig E / Eoff Robert L

Biochemistry. 2014 Oct. 21, v. 53, no. 41

2014

Abstract: Recent studies have identified human PrimPol as a new RNA/DNA primase and translesion DNA synthesis polymerase (TLS pol) that contributes to nuclear and mitochondrial DNA replication. We investigated the mechanism of PrimPol polymerase activity on both ... ...

Abstract	Recent studies have identified human PrimPol as a new RNA/DNA primase and translesion DNA synthesis polymerase (TLS pol) that contributes to nuclear and mitochondrial DNA replication. We investigated the mechanism of PrimPol polymerase activity on both undamaged and damaged DNA substrates. With MgÂ²âº as a cofactor, PrimPol binds primer-template DNA with low affinity Kd,DNA values (â¼200â1200 nM). DNA binding is enhanced 34-fold by MnÂ²âº (Kd,DNA = 27 nM). The pol activity of PrimPol is increased 400â1000-fold by MnÂ²âº compared to MgÂ²âº based on steady-state kinetic parameters. PrimPol makes a mistake copying undamaged DNA once every â¼100â2500 insertions events, which is comparable to other TLS pols, and the fidelity of PrimPol is â¼1.7-fold more accurate when MgÂ²âº is the cofactor compared to MnÂ²âº. PrimPol inserts dCMP opposite 8-oxo-dG with 2- (MnÂ²âº) to 6-fold (MgÂ²âº) greater efficiency than dAMP misinsertion. PrimPol-catalyzed dCMP insertion opposite 8-oxo-dG proceeds at â¼25% efficiency relative to unmodified template dG, and PrimPol readily extends from dC:8-oxo-dG base pairs (bps) with â¼2-fold greater efficiency than dA:8-oxo-dG bps. A tetrahydrofuran (THF) abasic-site mimic decreases PrimPol activity to â¼0.04%. In summary, PrimPol exhibits the fidelity typical of other TLS pols, is rather unusual in the degree of activation afforded by MnÂ²âº, and accurately bypasses 8-oxo-dG, a DNA lesion of special relevance to mitochondrial DNA replication and transcription.
Keywords	DNA replication ; DNA-directed DNA polymerase ; RNA ; humans ; magnesium ; manganese ; mitochondrial DNA ; tetrahydrofuran
Language	English
Dates of publication	2014-1021
Size	p. 6584-6594.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021%2Fbi501024u
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