Publications
Hovedinnhold
Ferrario E, Kallio JP, Strømland Ø, Ziegler M (2023): Novel calcium-binding motif stabilizes and increases the activity of Aspergillus fumigatus ecto-NADase. Biochemistry 62, doi: 10.1021/acs.biochem.3c00360.
Goyal S, Paspureddi A, Lu MJ, Chan HR, Lyons SN, Wilson CN, Niere M, Ziegler M, Cambronne XA (2023): Dynamics of SLC25A51 reveal preference for oxidized NAD+ and substrate led transport. EMBO Rep. 24, doi: 10.15252/embr.202256596.
Houry D, Raasakka A, Ferrario E, Niere M, Bifulco E, Kursula P, Ziegler M (2023): Identification of structural determinants of nicotinamide phosphoribosyl transferase (NAMPT) activity and substrate selectivity. J. Struct. Biol. 215, doi: 10.1016/j.jsb.2023.108004.
Kropotov A, Kulikova V, Solovjeva L, Yakimov A, Nerinovski K, Svetlova M, Sudnitsyna J, Plusnina A, Antipova M, Khodorkovskiy M, Migaud ME, Gambaryan S, Ziegler M, Nikiforov A (2022): Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. J. Biol. Chem. 298, doi: 10.1016/j.jbc.2022.102615.
Sharma S, Hsieh YC, Dietze J, Bockwoldt M, Strømland Ø, Ziegler M, Heiland I (2022): Early evolutionary selection of NAD biosynthesis pathway in bacteria. Metabolites 12, doi: 10.3390/metabo12070569.
Kristiansen CK, Chen A, Høyland LE, Ziegler M, Sullivan GJ, Bindoff LA, Liang KX (2022): Comparing the mitochondrial signatures in ESCs and iPSCs and their neural derivations. Cell Cycle 21, doi: 10.1080/15384101.2022.2092185.
Strømland Ø, Diab J, Ferrario E, Sverkeli LJ, Ziegler M (2021): The balance between NAD+ biosynthesis and consumption in ageing. Mech. Ageing. Dev. 199, doi: 10.1016/j.mad.2021.111569.
Lauritzen KH, Olsen MB, Ahmed MS, Yang K, Rinholm JE, Bergersen LH, Esbensen QY, Sverkeli LJ, Ziegler M, Attramadal H, Halvorsen B, Aukrust P, Yndestad A (2021): Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication. Elife 10, doi: 10.7554/eLife.59828.
Lüscher B, Ahel I, Altmeyer M, Ashworth A, Bai P, Chang P, Cohen M, Corda D, Dantzer F, Daugherty MD, Dawson TM, Dawson VL, Deindl S, Fehr AR, Feijs KLH, Filippov DV, Gagné JP, Grimaldi G, Guettler S, Hoch NC, Hottiger MO, Korn P, Kraus WL, Ladurner A, Lehtiö L, Leung AKL, Lord CJ, Mangerich A, Matic I, Matthews J, Moldovan GL, Moss J, Natoli G, Nielsen ML, Niepel M, Nolte F, Pascal J, Paschal BM, Pawłowski K, Poirier GG, Smith S, Timinszky G, Wang ZQ, Yélamos J, Yu X, Zaja R, Ziegler M (2021): ADP-ribosyltransferases, an update on function and nomenclature. FEBS J., doi: 10.1111/febs.16142.
Sverkeli LJ, Hayat F, Migaud ME, Ziegler M (2021): Enzymatic and chemical syntheses of Vacor analogs of nicotinamide riboside, NMN and NAD. Biomolecules 11, doi: 10.3390/biom11071044.
Ziegler M, Monné M, Nikiforov A, Agrimi G, Heiland I, Palmieri F (2021): Welcome to the Family: Identification of the NAD+ transporter of animal mitochondria as member of the solute carrier family SLC25. Biomolecules 11, doi: 10.3390/biom11060880.
Strømland Ø, Kallio JP, Pschibul A, Skoge RH, Harðardóttir HM, Sverkeli LJ, Heinekamp T, Kniemeyer O, Migaud ME, Makarov MV, Gossmann TI, Brakhage AA, Ziegler M (2021): Discovery of fungal surface NADases predominantly present in pathogenic species. Nat. Commun. 12, doi: 10.1038/s41467-021-21307-z.
Kropotov A, Kulikova V, Nerinovski K, Yakimov A, Svetlova M, Solovjeva L, Sudnitsyna J, Migaud ME, Khodorkovskiy M, Ziegler M, Nikiforov A (2021): Equilibrative nucleoside transporters mediate the import of nicotinamide riboside and nicotinic acid riboside into human cells. Int. J. Mol. Sci. 22, doi: 10.3390/ijms22031391.
Luongo TS, Eller JM, Lu M-J, Niere M, Raith F, Perry C, Bornstein MR, Oliphint P, Wang L, McReynolds MR, Migaud ME, Rabinowitz JD, Johnson FB, Johnsson K, Ziegler M, Cambronne XA, Baur JA (2020): SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature 588, doi: 10.1038/s41586-020-2741-7.
Liang KX, Kristiansen CK, Mostafavi S, Vatne GH, Zantingh GA, Kianian A, Tzoulis C, Høyland LE, Ziegler M, Megias Perez R, Furriol J, Zhang Z, Balafkan N, Hong Y, Siller R, Sullivan GJ, Bindoff LA (2020): Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations. EMBO. Mol. Med. 12, doi: 10.15252/emmm.202012146.
Ziegler M, Nikiforov AA (2020): NAD on the rise again. Nat. Metab. 2, doi: 10.1038/s42255-020-0197-6.
Gilmour BC, Gudmundsrud R, Frank J, Hov A, Lautrup S, Aman Y, Røsjø H, Brenner C, Ziegler M, Tysnes OB, Tzoulis C, Omland T, Søraas A, Holmøy T, Bergersen LH, Storm-Mathisen J, Nilsen H, Fang EF (2020): Targeting NAD+ in translational research to relieve diseases and conditions of metabolic stress and ageing. Mech. Ageing Dev. 186, doi: 10.1016/j.mad.2020.111208.
Kulikova V, Shabalin K, Nerinovski K, Yakimov A, Svetlova M, Solovjeva L, Kropotov A, Khodorkovskiy M, Migaud ME, Ziegler M, Nikiforov A (2019): Degradation of extracellular NAD+ intermediates in cultures of human HEK293 cells. Metabolites 9, doi:10.3390/metabo9120293.
Bockwoldt M, Houry D, Niere M, Gossmann TI, Reinartz I, Schug A, Ziegler M, Heiland I (2019): Identification of evolutionary and kinetic drivers of NAD-dependent signaling. Proc. Natl. Acad. Sci. U. S. A. 116, doi: 10.1073/pnas.1902346116.
Lee YG, Reader BF, Herman D, Streicher A, Englert JA, Ziegler M, Chung S, Karpurapu M, Park GY, Christman JW, Ballinger MN (2019): Sirtuin 2 enhances allergic asthmatic inflammation. JCI Insight 4, doi: 10.1172/jci.insight.124710.
Strømland Ø, Niere M, Nikiforov AA, VanLinden MR, Heiland I, Ziegler M (2019): Keeping the balance in NAD metabolism. Biochem. Soc. Trans. 47, doi: 10.1042/BST20180417. Review
Shabalin K, Nerinovski K, Yakimov A, Kulikova V, Svetlova M, Solovjeva L, Khodorkovskiy M, Gambaryan S, Cunningham R, Migaud ME, Ziegler M, Nikiforov A (2018): NAD Metabolome Analysis in Human Cells Using ¹H NMR Spectroscopy. Int. J. Mol. Sci. 19, doi: 10.3390/ijms19123906.
Varland S, Aksnes H, Kryuchkov F, Impens F, Van Haver D, Jonckheere V, Ziegler M, Gevaert K, Van Damme P, Arnesen T (2018): N-terminal Acetylation Levels Are Maintained During Acetyl-CoA Deficiency in Saccharomyces cerevisiae. Mol. Cell. Proteomics 17, doi: 10.1074/mcp.RA118.000982.
Buonvicino D, Mazzola F, Zamporlini F, Resta F, Ranieri G, Camaioni E, Muzzi M, Zecchi R, Pieraccini G, Dölle C, Calamante M, Bartolucci G, Ziegler M, Stecca B, Raffaelli N, Chiarugi A (2018): Identification of the nicotinamide salvage pathway as a new toxification route for antimetabolites. Cell. Chem. Biol. 25, doi: 10.1016/j.chembiol.2018.01.012.
VanLinden MR, Niere M, Nikiforov AA, Ziegler M, Dölle C (2017): Compartment-specific poly-ADP-ribose formation as a biosensor for subcellular NAD pools. Methods Mol. Biol. 1608, doi: 10.1007/978-1-4939-6993-7_4.
Skoge RH, Ziegler M (2016): SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6. J. Cell Sci. 129, doi: 10.1242/jcs.187518.
VanLinden MR, Dölle C, Pettersen IK, Kulikova VA, Niere M, Agrimi G, Dyrstad SE, Palmieri F, Nikiforov AA, Tronstad KJ, Ziegler M (2015): Subcellular distribution of NAD+ between cytosol and mitochondria determines the metabolic profile of human cells. J. Biol. Chem. 290, doi: 10.1074/jbc.M115.654129.
Kulikova V, Shabalin K, Nerinovski K, Dölle C, Niere M, Yakimov A, Redpath P, Khodorkovskiy M, Migaud ME, Ziegler M, Nikiforov A (2015): Generation, release, and uptake of the NAD precursor nicotinic acid riboside by human cells. J. Biol. Chem. 290, doi: 10.1074/jbc.M115.664458.
Nikiforov A, Kulikova V, Ziegler M (2015): The human NAD metabolome: Functions, metabolism and compartmentalization. Crit. Rev. Biochem. Mol. Biol. 50, doi: 10.3109/10409238.2015.1028612. Review
Aksnes H, Van Damme P, Goris M, Starheim KK, Marie M, Støve SI, Hoel C, Kalvik TV, Hole K, Glomnes N, Furnes C, Ljostveit S, Ziegler M, Niere M, Gevaert K, Arnesen T (2015): An organellar nα-acetyltransferase, naa60, acetylates cytosolic N-termini of transmembrane proteins and maintains Golgi integrity. Cell Rep. 10, doi: 10.1016/j.celrep.2015.01.053.
Love NR, Pollak N, Dölle C, Niere M, Chen Y, Oliveri P, Amaya E, Patel S, Ziegler M (2015): NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms. Proc. Natl. Acad. Sci. U. S. A. 112, doi: 10.1073/pnas.1417290112.
Rack JG, Lutter T, Kjæreng Bjerga GE, Guder C, Ehrhardt C, Värv S, Ziegler M, Aasland R (2014): The PHD finger of p300 influences its ability to acetylate histone and non-histone targets. J. Mol. Biol. 426, doi: 10.1016/j.jmb.2014.08.011.
Gossmann TI, Ziegler M (2014): Sequence divergence and diversity suggests ongoing functional diversification of vertebrate NAD metabolism. DNA Repair (Amst.) 23, doi: 10.1016/j.dnarep.2014.07.005.
Blacker TS, Mann ZF, Gale JE, Ziegler M, Bain AJ, Szabadkai G, Duchen MR (2014): Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nat. Commun. 29, doi: 10.1038/ncomms4936.
Skoge RH, Dölle C, Ziegler M (2014): Regulation of SIRT2-dependent α-tubulin deacetylation by cellular NAD levels. DNA Repair (Amst.) 23, doi: 10.1016/j.dnarep.2014.04.011.
Love NR, Ziegler M, Chen Y, Amaya E (2014): Carbohydrate metabolism during vertebrate appendage regeneration: What is its role? How is it regulated?: A postulation that regenerating vertebrate appendages facilitate glycolytic and pentose phosphate pathways to fuel macromolecule biosynthesis. Bioessays 36, doi: 10.1002/bies.201300110.
Rack JG, VanLinden MR, Lutter T, Aasland R, Ziegler M (2014): Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform. J. Mol. Biol. 426, doi: 10.1016/j.jmb.2013.10.027.
Dölle C, Skoge RH, Vanlinden MR, Ziegler M (2013): NAD biosynthesis in humans - Enzymes, metabolites and therapeutic aspects. Curr. Top. Med. Chem. 13, doi: 10.2174/15680266113136660206. Review
Stavrum AK, Heiland I, Schuster S, Puntervoll P, Ziegler M (2013): Model of tryptophan metabolism, readily scalable using tissue-specific gene expression data. J. Biol. Chem. 288, doi: 10.1074/jbc.M113.474908.
Koch-Nolte F, Ziegler M (2013): Physiology of ADP-ribosylation. FEBS J. 280, doi: 10.1111/febs.12389. Review
Schüler H, Ziegler M (2013): Pharmacology of ADP-ribosylation. FEBS J. 280, doi: 10.1111/febs.12388. Review
Dölle C, Rack JG, Ziegler M (2013): NAD and ADP-ribose metabolism in mitochondria. FEBS J. 280, doi: 10.1111/febs.12304. Review
Chiarugi A, Dölle C, Felici R, Ziegler M (2012): The NAD metabolome - A key determinant of cancer cell biology. Nat. Rev. Cancer 12, doi: 10.1038/nrc3340. Review
Niere M, Mashimo M, Agledal L, Dölle C, Kasamatsu A, Kato J, Moss J, Ziegler M (2012): ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase (PARG) isoforms, is responsible for degradation of mitochondrial matrix-associated poly(ADP-ribose). J. Biol. Chem. 287, doi: 10.1074/jbc.M112.349183.
Gossmann TI, Ziegler M, Puntervoll P, de Figueiredo LF, Schuster S, Heiland I (2012): NAD(+) biosynthesis and salvage - A phylogenetic perspective. FEBS J. 279, doi: 10.1111/j.1742-4658.2012.08559.x
de Figueiredo LF, Gossmann TI, Ziegler M, Schuster S (2011): Pathway analysis of NAD+ metabolism. Biochem J. 439, doi: 10.1042/BJ20110320.
Hottiger MO, Boothby M, Koch-Nolte F, Lüscher B, Martin NM, Plummer R, Wang ZQ, Ziegler M (2011): Progress in the function and regulation of ADP-Ribosylation. Sci. Signal. 4, doi: 10.1126/scisignal.2001645. Meeting report
Nikiforov A, Dölle C, Niere M, Ziegler M (2011): Pathways and subcellular compartmentation of NAD biosynthesis in human cells: From entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 286, doi: 10.1074/jbc.M110.213298.
Koch-Nolte F, Fischer S, Haag F, Ziegler M (2011): Compartmentation of NAD+-dependent signalling. FEBS Lett. 585, doi: 10.1016/j.febslet.2011.03.045. Review
Lau C, Dölle C, Gossmann TI, Agledal L, Niere M, Ziegler M (2010): Isoform-specific targeting and interaction domains in human nicotinamide mononucleotide adenylyltransferases. J. Biol. Chem. 285, doi: 10.1074/jbc.M110.107631.
Agledal L, Niere M, Ziegler M (2010): The phosphate makes a difference: Cellular functions of NADP. Redox Rep. 15, doi: 10.1179/174329210X12650506623122. Review
Dölle C, Niere M, Lohndal E, Ziegler M (2010): Visualization of subcellular NAD pools and intra-organellar protein localization by poly-ADP-ribose formation. Cell. Mol. Life Sci. 67, doi: 10.1007/s00018-009-0190-4.
Evjenth R, Hole K, Karlsen OA, Ziegler M, Arnesen T, Lillehaug JR (2009): Human Naa50p (Nat5/San) displays both protein N alpha- and N epsilon-acetyltransferase activity. J. Biol. Chem. 284, doi: 10.1074/jbc.M109.001347.
Evjenth R, Hole K, Ziegler M, Lillehaug JR (2009): Application of reverse-phase HPLC to quantify oligopeptide acetylation eliminates interference from unspecific acetyl CoA hydrolysis. BMC Proc. 3 Suppl. 6, doi: 10.1186/1753-6561-3-S6-S5.
Lau C, Niere M, Ziegler M (2009): The NMN/NaMN adenylyltransferase (NMNAT) protein family. Front. Biosci. 14, doi: 10.2741/3252. Review
Kellmann R, Schaffner CA, Grønset TA, Satake M, Ziegler M, Fladmark KE (2009): Proteomic response of human neuroblastoma cells to azaspiracid-1. J. Proteomics 72, doi: 10.1016/j.jprot.2009.02.008.
Martino F, Kueng S, Robinson P, Tsai-Pflugfelder M, van Leeuwen F, Ziegler M, Cubizolles F, Cockell MM, Rhodes D, Gasser SM (2009): Reconstitution of yeast silent chromatin: Multiple contact sites and O-AADPR binding load SIR complexes onto nucleosomes in vitro. Mol. Cell. 33, doi: 10.1016/j.molcel.2009.01.009.
Koch-Nolte F, Haag F, Guse AH, Lund F, Ziegler M (2009): Emerging roles of NAD+ and its metabolites in cell signaling. Sci. Signal. 2, doi: 10.1126/scisignal.257mr1. Review
Dölle C, Ziegler M (2009): Application of a coupled enzyme assay to characterize nicotinamide riboside kinases. Anal. Biochem. 385, doi: 10.1016/j.ab.2008.10.033.
Niere M, Kernstock S, Koch-Nolte F, Ziegler M (2008): Functional localization of two poly(ADP-ribose)-degrading enzymes to the mitochondrial matrix. Mol Cell Biol. 28, doi: 10.1128/MCB.01766-07.
Lewis AM, Masgrau R, Vasudevan SR, Yamasaki M, O'Neill JS, Garnham C, James K, Macdonald A, Ziegler M, Galione A, Churchill GC (2007): Refinement of a radioreceptor binding assay for nicotinic acid adenine dinucleotide phosphate. Anal. Biochem. 371, doi: 10.1016/j.ab.2007.08.030.
Pollak N, Niere M, Ziegler M (2007): NAD kinase levels control the NADPH concentration in human cells. J. Biol. Chem. 282, doi: 10.1074/jbc.M704442200.
Billington RA, Bruzzone S, De Flora A, Genazzani AA, Koch-Nolte F, Ziegler M, Zocchi E (2006): Emerging functions of extracellular pyridine nucleotides. Mol. Med. 12, doi: 10.2119/2006–00075.Billington. Review
Berger F, Lau C, Ziegler M (2007): Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1. Proc. Natl. Acad. Sci. U. S. A. 104, doi: 10.1073/pnas.0609211104.
Pollak N, Dölle C, Ziegler M (2007): The power to reduce: Pyridine nucleotides - Small molecules with a multitude of functions. Biochem. J. 402, doi: 10.1042/BJ20061638. Review
Churamani D, Dickinson GD, Ziegler M, Patel S (2006): Time sensing by NAADP receptors. Biochem J. 397, doi: 10.1042/BJ20060179.
Ziegler M (2005): A vital link between energy and signal transduction. FEBS J. 272, doi: 10.1111/j.1742-4658.2005.04893.x. Review
Berger F, Lau C, Dahlmann M, Ziegler M (2005): Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. J. Biol. Chem. 280, doi: 10.1074/jbc.M508660200.
Oei SL, Keil C, Ziegler M (2005): Poly(ADP-ribosylation) and genomic stability. Biochem. Cell. Biol. 83, doi: 10.1139/o05-039. Review
Ziegler M, Niere M (2004): NAD+ surfaces again. Biochem. J. 382, doi: 10.1042/BJ20041217. Commentary
Berger F, Ramírez-Hernández MH, Ziegler M (2004): The new life of a centenarian: Signalling functions of NAD(P). Trends Biochem. Sci. 29, doi: 10.1016/j.tibs.2004.01.007. Review
Petermann E, Ziegler M, Oei SL (2003): ATP-dependent selection between single nucleotide and long patch base excision repair. DNA Repair (Amst.) 2, doi: 10.1016/S1568-7864(03)00117-4.
Werner E, Ziegler M, Lerner F, Schweiger M, Heinemann U (2002): Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN. FEBS Lett. 516, doi: 10.1016/S0014-5793(02)02556-5.
Werner E, Ziegler M, Lerner F, Schweiger M, Muller YA, Heinemann U (2002): Crystallization and preliminary X-ray analysis of human nicotinamide mononucleotide adenylyltransferase (NMNAT). Acta Crystallogr. D Biol. Crystallogr. 58, doi:10.1107/S0907444901017437.
Herrero-Yraola A, Bakhit SM, Franke P, Weise C, Schweiger M, Jorcke D, Ziegler M (2001): Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria. EMBO J. 20, doi: 10.1093/emboj/20.10.2404.
Lerner F, Niere M, Ludwig A, Ziegler M (2001): Structural and functional characterization of human NAD kinase. Biochem. Biophys. Res. Commun. 288, doi: 10.1006/bbrc.2001.5735.
Ziegler M, Oei SL (2001): A cellular survival switch: poly(ADP-ribosyl)ation stimulates DNA repair and silences transcription. Bioessays 23, doi: 10.1002/bies.1074. Review.
Schweiger M, Hennig K, Lerner F, Niere M, Hirsch-Kauffmann M, Specht T, Weise C, Oei SL, Ziegler M (2001). Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis. FEBS Lett. 492, doi: 10.1016/S0014-5793(01)02180-9.
Oei SL, Ziegler M (2000). ATP for the DNA ligation step in base excision repair is generated from poly(ADP-ribose). J. Biol. Chem. 275, doi: 10.1074/jbc.m002429200.
Mayer-Kuckuk P, Ullrich O, Ziegler M, Grune T, Schweiger M (1999): Functional interaction of poly(ADP-ribose) with the 20S proteasome in vitro. Biochem. Biophys. Res. Commun. 259, doi: 10.1006/bbrc.1999.0824.
Jorcke D, Ziegler M, Herrero-Yraola A, Schweiger M (1998): Enzymic, cysteine-specific ADP-ribosylation in bovine liver mitochondria. Biochem. J. 332, doi:10.1042/bj3320189.
Oei SL, Griesenbeck J, Schweiger M, Ziegler M (1998). Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors. J. Biol. Chem. 273, doi: 10.1074/jbc.273.48.31644.
Ziegler M, Jorcke D, Schweiger M (1997): Identification of bovine liver mitochondrial NAD+ glycohydrolase as ADP-ribosyl cyclase. Biochem J. 326, doi: 10.1042/bj3260401.
Ziegler M, Jorcke D, Schweiger M (1997): Metabolism of cyclic ADP-ribose: a new role for NAD+ glycohydrolases. Rev. Physiol. Biochem. Pharmacol. 131, doi: 10.1007/3-540-61992-5_6. Review.
Griesenbeck J, Oei SL, Mayer-Kuckuk P, Ziegler M, Buchlow G, Schweiger M (1997): Protein-protein interaction of the human poly(ADP-ribosyl)transferase depends on the functional state of the enzyme. Biochemistry 36, doi: 10.1021/bi962710g.
Oei SL, Griesenbeck J, Buchlow G, Jorcke D, Mayer-Kuckuk P, Wons T, Ziegler M (1996). NAD+ analogs substituted in the purine base as substrates for poly(ADP-ribosyl) transferase. FEBS Lett. 397, doi: 10.1016/s0014-5793(96)01137-4.
Ziegler M, Jorcke D, Zhang J, Schneider R, Klocker H, Auer B, Schweiger M (1996). Characterization of detergent-solubilized beef liver mitochondrial NAD+ glycohydrolase and its truncated hydrosoluble form. Biochemistry 35, doi: 10.1021/bi9527698.