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Faculty of Biology, Chemistry & Earth Sciences

Biochemistry I – Prof. Dr. Clemens Steegborn vertreten durch Prof. Dr. Ulrich Krauß

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Publications

 

Research publications

105) Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, Huggins DJ, Steegborn C, Miranda IC, Meinke PT, Buck J, Levin LR (2023). On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun. 14(1):637. doi: 10.1038/s41467-023-36119-6.<PubMed>

104) Miller M, Rossetti T, Ferreira J, Ghanem L, Balbach M, Kaur N, Levin LR, Buck J, Kehr M, Coquille S, van den Heuvel J, Steegborn C, Fushimi M, Finkin-Groner E, Myers RW, Kargman S, Liverton NJ, Huggins DJ, Meinke PT. Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates. J Med Chem. 65(22):15208-15226. doi: 10.1021/acs.jmedchem.2c01133. <PubMed>

103) Weiss S, Adolph RS, Schweimer K, DiFonzo A, Meleshin M, Schutkowski M, Steegborn C (2022) Molecular Mechanism of Sirtuin 1 Modulation by the AROS Protein. Int J Mol Sci 23(23):12764 DOI: 10.3390/ijms232112764 <PubMed>

102) Rossetti T, Ferreira J, Ghanem L, Buck H, Steegborn C, Myers RW, Meinke PT, Levin LR, Buck J (2022) Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential. Front Physiol.13:1013845. doi: 10.3389 <PubMed>

101) Suenkel B, Valente S, Zwergel C, Weiss S, Di Bello E, Fioravanti R, Aventaggiato M, Amorim JA, Garg N, Kumar S, Lombard DB, Hu T, Singh PK, Tafani M, Palmeira CM, Sinclair D, Mai A, Steegborn C (2022) Potent and Specific Activators for Mitochondrial Sirtuins Sirt3 and Sirt5. J Med Chem 65(20):14015-14031.doi: 10.1021/acs.jmedchem.2c01215. Epub 2022 Oct 13.<PubMed>

100) Rodriguez-Ruiz A, Braun D, Pflug S, Brol A, Sylvester M, Steegborn C, Schweizer U (2022) Insights into the Mechanism of Human Deiodinase 1. Int J Mol Sci. 23(10):5361. doi: 10.3390/ijms23105361.<PubMed>

99) Ip J, Xu L, Dai J, Steegborn C, Jaffré F, Evans T, Jim Cheung, Basson C, Panaghie G, Krogh-Madsen T, Abbott G,  Lerman B (2021) Constitutively Activating GNAS Somatic Mutation in Right Ventricular Outflow Tract Tachycardia. Circulation: Arrhythmia and Electrophysiology 14(10):e010082. doi: 10.1161/CIRCEP.121.010082. Epub 2021 Sep 30. <PubMed>

 

98) Fushimi M, Buck H, Balbach M, Gorovyy A, Ferreira J, Rossetti T, Kaur N, Levin LR, Buck J, Quast J, van den Heuvel J, Steegborn C, Finkin-Groner E, Kargman S, Michino M, Foley MA, Miller M, Liverton NJ, Huggins DJ, Meinke PT. (2021) Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10) ACS Med Chem Lett 12(8):1283-1287.doi: 10.1021/acsmedchemlett.1c00273. eCollection 2021 Aug 12. <PubMed>

 

97) Hu T, Shukla SK, Vernucci E, He C, Wang D, King RJ, Jha K, Siddhanta K, Mullen NJ, Attri KS, Murthy D, Chaika NV, Thakur R, Mulder SE, Pacheco CG, Fu X, High RR, Yu F, Lazenby A, Steegborn C, Lan P, Mehla K, Rotili D, Chaudhary S, Valente S, Tafani M, Mai A, Auwerx J, Verdin E, Tuveson D, Singh PK. (2021) Metabolic Rewiring by Loss of Sirt5 Promotes Kras-Induced Pancreatic Cancer Progression. Gastroenterology 2021 Jul 8;S0016-5085(21)03159-0.doi: 10.1053/j.gastro.2021.06.045. Online ahead of print <PubMed>


96) Reif A, Lam K, Weidler S, Lott M, Boos I, Lokau J, Bretscher C, Mönnich M, Perkams L, Schmälzlein M, Graf C, Fischer JP, Lechner C, Hallstein K, Becker S, Weyand M, Steegborn C, Schultheiss G, Rose-John S, Garbers C, Unverzagt C. (2021) Natural Glycoforms of Human Interleukin 6 show atypical plasma clearance. Angew Chem Int Ed Engl. 60(24):13380-13387. doi: 10.1002/anie.202101496. <PubMed>

 

95) You W, Steegborn C (2021) Binding site for activator MDL-801 on SIRT6. Nat Chem Biol. 17(5):519-521. doi: 10.1038/s41589-021-00749-y. <PubMed>

 

94) You W, Steegborn C (2020) Structural Basis for Activation of Human Sirtuin 6 by Fluvastin. ACS Med Chem Lett.11(11) 2285-2289 <PubMed>

 

93) Kleinbölting S, Miehling J, Steegborn C (2020) Crystal structure and enzymatic characterization of the putative adenylyl cyclase HpAC1 from Hippeastrum reveal dominat triphosphosphatase activity. J Struc Biol 212(3):107649 <PubMed>

 

92) Linder J, Hupfeld E, Weyand M, Steegborn C, Moniot S (2020) Crystal structure of a class III adenylyl cyclase-like ATP-binding protein from Pseudomonas aeruginosa. J Struct Biol 211(2): 107534 <PubMed>

 

91) Teodoro JS, Amorim JA, Machado IF, Castela AC, Steegborn C, Sinclair DA, Rolo AP, Palmeira CM. (2020) The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function.Int J Mol Sci <PubMed>

 

90) Tomassi S, Pfahler J, Mautone N, Rovere A, Esposito C, Passeri D, Pellicciari R, Novellino E, Pannek M, Steegborn C, Paiardini A, Mai A, Rotili D. (2020) From PARP1 to TNKS2 Inhibition: A Structure-Based Approach. ACS Med Chem Lett 11(5):862-868 <PubMed>

 

89) You W, Zheng W, Weiss S, Chua KF, Steegborn C (2019) Structural basis for the activation and inhibition of Sirtiun 6 by quercetin and its derivatives. Sci Rep 9, 19176.<PubMed>

 

88) Weber AM, Kaiser J, Ziegler T, Pilsl S, Renzl C, Sixt L , Pietruschka G, Moniot S, Kakoti A, Juraschitz M, Schrottke S, Lledo Bryant L, Steegborn C,  Bittl R, Mayer G, Möglich A (2019) A blue light receptor that mediates RNA binding and translational regulation. Nat.Chem.Biol. 15, 1085-1092.<PubMed>

 

87) Pinto A, El Ali Z, Moniot S, Tamborini L, Steegborn C, Foresti R, De Micheli C (2018) Effects of 3-Bromo-4,5-dihydroisoxazole Derivatives on Nrf2 Activation and Heme Oxygenase-1 Expression. ChemistryOpen 7, 858-864.<PubMed>

 

86) You W, Steegborn C (2018) Structural Basis of Sirtuin 6 Inhibition by the Hydroxamate Trichostatin A: Implications for Protein Deacylase Drug Development. J. Med. Chem. 61, 10922-10928.<PubMed>

 

85) Iachettini S, Trisciuoglio D, Rotili D, Lucidi A, Salvati E, Zizza P, Di Leo L, Del Bufalo D, Ciriolo MR, Leonetti C, Steegborn C, Mai A, Rizzo A, Biroccio A (2018) Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells. Cell Death Dis. 9, 996. <PubMed>

 

84) Kalbas D, Liebscher S, Nowak T, Meleshin M, Pannek M, Popp C, Alhalabi Z, Bordusa F, Sippl W, Steegborn C, Schutkowski M (2018) Potent and Selective Inhibitors of Human Sirtuin 5. J. Med. Chem. 61, 2460-2471.<PubMed>

 

83) Pannek M, Simic Z, Fuszard M, Meleshin M, Rotili D, Mai A, Schutkowski M, Steegborn C (2017) Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features. Nat. Commun. 8,1513.<PubMed>

 

82) Rajabi N, Auth M, Troelsen KR, Pannek M, Bhatt D, Fontenas M, Hirshey MD, Steegborn C, Madsen AS, Olsen CA (2017) Mechanism-based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural, and Kinetic Insight. Angew. Chem. Int. Ed. Engl. 56, 14836-14841.<PubMed>

 

81) Quinti L, Dayalan Naidu S, Träger U, Chen X, Kegel-Gleason K, Llères D, Connolly C, Chopra V, Low C, Moniot S, Sapp E, Tousley AR, Vodicka P, Van Kanegan MJ, Kaltenbach LS, Crawford LA, Fuszard M, Higgins M, Miller JRC, Farmer RE, Potluri V, Samajdar S, Meisel L, Zhang N, Snyder A, Stein R, Hersch SM, Ellerby LM, Weerapana E, Schwarzschild MA, Steegborn C, Leavitt BR, Degterev A, Tabrizi SJ, Lo DC, DiFiglia M, Thompson LM, Dinkova-Kostova AT, Kazantsev AG (2017) A KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington disease patients. Proc. Natl Acad. Sci. USA 114, E4676-E4685.<PubMed>

 

80) Graf CGF, Schulz C , Schmälzlein M, Heinlein C, Mönnich M, Perkams L, Püttner M, Boos I, Hessefort M, Lombana Sanchez JN, Weyand M, Steegborn C, Breiden B, Ross K, Schwarzmann G, Sandhoff K, Unverzagt C (2017) Synthetic Glycoforms reveal Carbohydrate-Dependent Bioactivity of Human Saposin D. Angew. Chem. Int. Ed. Engl. 56, 5252-5257.<PubMed>

 

79) Li J, Bonkowski MS, Moniot S, Zhang D, Hubbard BP, Ling AJ, Rajman LA, Qin B, Lou Z, Gorbunova V, Aravind L, Steegborn C, Sinclair DA (2017) A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science 355, 1312-1317.<PubMed>

 

78) de Oliveira RM, Vicente Miranda H, Francelle L, Pinho R, Szegö ÉM, Martinho R, Munari F, Lázaro DF, Moniot S, Guerreiro P, Fonseca L, Marijanovic Z, Antas P, Gerhardt E, Enguita FJ, Fauvet B, Penque D, Pais TF, Tong Q, Becker S, Kügler S, Lashuel HA, Steegborn C, Zweckstetter M, Outeiro TF (2017) The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. PLoS Biol. 2017 15:e2000374.<PubMed>

 

77) Moniot S, Forgione M, Lucidi A, Hailu GS, Nebbioso A, Carafa V, Baratta F, Altucci L, Giacché N, Passeri D, Pellicciari R, Mai A, Steegborn C, Rotili D (2017) Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure-Activity Relationship, X-ray Crystal Structure, and Anticancer Activity. J. Med. Chem. 60, 2344-2360.<PubMed>

 

76) Sundriyal S, Moniot S, Mahmud Z, Yao S, Di Fruscia P, Reynolds CR, Dexter DT, Sternberg MJ, Lam EW, Steegborn C, Fuchter MJ (2017) Thienopyrimidinone Based Sirtuin-2 (SIRT2)-Selective Inhibitors Bind in the Ligand Induced Selectivity Pocket. J. Med. Chem. 60, 1928-1945.<PubMed>

 

75) You W, Rotili D, Li TM, Kambach C, Meleshin M, Schutkowski M, Chua KF, Mai A, Steegborn C. (2017) Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules. Angew. Chem. Int. Ed. Engl. 56, 1007-1011.<PubMed>

 

74) L. Ramos-Espiritu, S. Kleinboelting, F.A. Navarrete, A. Alvau, P.E. Visconti, F. Valsecchi, A. Starkov, G. Manfredi, H. Buck, C. Adura, J.H. Zippin, J. van den Heuvel, J.F. Glickman, C. Steegborn, L.R. Levin, J. Buck (2016) Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase. Nature Chem. Biol. 12, 838-44.

 

73) L. Quinti, M. Casale, S. Moniot, T.F. Pais, L.S. Kaltenbach, J. Pallos, R.G. Lim, S.D. Naidu, H. Runne, L. Meisel, N.A. Rauf, D. Leyfer, M.M. Maxwell, E. Saiah, J.E. Landers, R. Luthi-Carter, R. Abagyan, A.T. Dinkova-Kostova, C. Steegborn, J.L. Marsh, D.C. Lo, L.M. Thompson, A.G. Kazantsev (2016) SIRT2- and NRF2-targeting thiazole-containing compound with therapeutic activity in Huntington's disease models. Cell Chem. Biol. 23, 849-61.

 

72) Kleinboelting S, Ramos-Espiritu L, Buck H, Colis L, van den Heuvel J, Glickman JF, Levin LR, Buck J, Steegborn C (2016) Bithionol Potently Inhibits Human Soluble Adenylyl Cyclase through Binding to the Allosteric Activator Site. J. Biol. Chem. 291, 9776-9784.

 

71) Schuster S, Roessler C, Meleshin M, Zimmermann P, Simic Z, Kambach C, Schiene-Fischer C, Steegborn C, Hottiger MO, Schutkowski M. (2016) A continuous sirtuin activity assay without any coupling to enzymatic or chemical reactions. Sci. Rep. 6:22643.

 

70) Valente S, Mellini P, Spallotta F, Carafa V, Nebbioso A, Polletta L, Carnevale I, Saladini S, Trisciuoglio D, Gabellini C, Tardugno M, Zwergel C, Cencioni C, Atlante S, Moniot S, Steegborn C, Budriesi R, Tafani M, Del Bufalo D, Altucci L, Gaetano C, Mai A. (2016) 1,4-Dihydropyridines Active on the SIRT1/AMPK Pathway Ameliorate Skin Repair and Mitochondrial Function and Exhibit Inhibition of Proliferation in Cancer Cells. J. Med. Chem. 59, 1471-1491.

 

69) U. Schweizer & C. Steegborn (2015) Thyroid hormones—From Crystal Packing to Activity to Reactivity. Angew. Chem. Int. Ed. Engl. 54, 12856-8.

 

68) Z. Simic, M. Weiwad, A. Schierhorn, C. Steegborn, M. Schutkowski (2015) The ɛ-amino group of protein lysine residues is highly susceptible to nonenzymatic acylation by several physiological acyl-CoA thioesters. ChemBioChem, 16, 2337-47.

 

67) C. Roessler, C. Tueting, M. Meleshin, D. Rauh, C. Steegborn, M. Schutkowski (2015) A novel continuous assay for the deacylase Sirtuin 5 and other deacetylases. J. Med. Chem. 58, 7217-23.

 

66) A. Banerjee, R.S. Adolph, J. Gopalakrishnapai, S. Kleinboelting, C. Emmerich, C. Steegborn, S.S. Visweswariah (2015) A Universal Stress Protein (USP) in Mycobacteria binds cAMP. J. Biol. Chem. 290, 12731-43.

 

65) L. Polletta, E. Vernucci, I. Carnevale, T. Arcangeli, D. Rotili, S. Palmerio, C. Steegborn, T. Nowak, M. Schutkowski, L. Pellegrini, L. Sansone, L. Villanova, A. Runci, B. Pucci, E. Morgante, M. Fini, A. Mai, M. A. Russo, M. Tafani (2015). SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy 11, 253-70.

 

64) T. Rumpf, M. Schiedel, B. Karaman, C. Roessler, B.J. North, A. Lehotzky, J. Oláh, K.I. Ladwein, K. Schmidtkunz, M. Gajer, M. Pannek, C. Steegborn, D.A. Sinclair, S. Gerhardt, J. Ovádi, M. Schutkowski, W. Sippl, O. Einsle, M. Jung (2015). Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat. Commun. 6:6263

 

63) X. Chen, P. Wales, L. Quinti, F. Zuo, S. Moniot, F. Herisson, N.A. Rauf, H. Wang, R.B. Silverman, C. Ayata, M.M. Maxwell, C. Steegborn, M.A. Schwarzschild, T.F. Outeiro, A.G. Kazantsev (2015). The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson's Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia. PLoS One 10, e0116919

 

62) P. Di Fruscia, E. Zacharioudakis, C. Liu, S. Moniot, S. Laohasinnarong, M. Khongkow, I.F. Harrison, K. Koltsida, C.R. Reynolds, K. Schmidtkunz, M. Jung, K.L. Chapman, C. Steegborn, D.T. Dexter, M.J. Sternberg, E.W. Lam, M.J. Fuchter (2014) The Discovery of a Highly Selective 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson's Disease Model. ChemMedChem 10, 69-82.

 

61) B. Fränzel, F. Fischer, C. Steegborn, D.A. Wolters (2014) Proteinase K improves quantitative acylation studies. Proteomics 15, 44-7.

 

60) Roessler C, Nowak T, Pannek M, Gertz M, Nguyen GT, Scharfe M, Born I, Sippl W, Steegborn C, Schutkowski M. (2014) Chemical Probing of the Human Sirtuin 5 Active Site Reveals Its Substrate Acyl Specificity and Peptide-Based Inhibitors. Angew. Chem. Int. Ed. 53, 10728-32.

 

59) S. Kleinboelting, J. van den Heuvel, C. Steegborn (2014) Structural analysis of human soluble adenylyl cyclase and crystal structures of its nucleotide complexes - implications for cyclase catalysis and evolution. FEBS J. 281, 4151-64.

 

58) U. Schweizer, C. Schlicker, D. Braun, J. Köhrle, C. Steegborn (2014) Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism. Proc. Natl Acad. Sci. USA 111, 10526-31.

 

57) M.H. Suhre, T. Scheibel, C. Steegborn, M. Gertz (2014) Crystallization and preliminary X-ray diffraction analysis of proximal thread matrix protein 1 (PTMP1) from Mytilus galloprovincialis. Acta Crystallogr. Sect. F 70, 769-72.

 

56) S. Kleinboelting, J. van den Heuvel, C. Kambach, M. Weyand, M. Leipelt, C. Steegborn (2014) Expression, purification, crystallization and preliminary X-ray diffraction analysis of a mammalian type 10 adenylyl cyclase. Acta Crystallogr. Sect. F 70, 467-9.

 

55) M.H. Suhre, M. Gertz, C. Steegborn, T. Scheibel (2014) Structural and functional features of a collagen-binding matrix protein from the mussel byssus. Nat. Commun. 5:3392.

 

54) S. Kleinboelting, A. Diaz, S. Moniot, J. van den Heuvel, M. Weyand, L.R. Levin, J. Buck, C. Steegborn (2014) Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate. Proc. Natl Acad. Sci. USA 111, 3727-32.

 

53) G.T.T. Nguyen, S. Schaefer, M. Gertz, M. Weyand, C. Steegborn (2013) Crystal structures of Sirt3 complexes with the resveratrol derivative 5-(2-(4-bromophenyl)vinyl)-1,3-benzenediol reveal binding sites and inhibition mechanism. Chem. Biol. 20:1375-85.

 

52) D. Rauh, F. Fischer, M. Gertz, M. Lakshminarasimhan, T. Bergbrede, F. Aladini, C. Kambach, C.F.W. Becker, J. Zerweck, M. Schutkowski, C. Steegborn (2013). An acetylome peptide microarray reveals specificities and deacetylation substrates for all human Sirtuin isoforms. Nat. Commun. 4:2327.

 

51) G.T.T. Nguyen, S. Schaefer, M. Gertz, M. Weyand, C. Steegborn (2013) Structures of human sirtuin 3 complexes with ADP-ribose and with carba-NAD+ and SRT1720: binding details and inhibition mechanism. Acta Cryst. D 69, 1423-32.

 

50) M. Gertz, F. Fischer, G.T.T. Nguyen, M. Lakshminarasimhan, M. Schutkowski, M. Weyand, C. Steegborn (2013) Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism. Proc. Natl Acad. Sci. USA 110:E2772-81.

 

49) G. Laurent, N.J. German, A.K. Saha, V.C. de Boer, M. Davies, T.R. Koves, N. Dephoure, F. Fischer, G. Boanca, B. Vaitheesvaran, S.B. Lovitch, A.H. Sharpe, I.J. Kurland, C. Steegborn, S.P. Gygi, D.M. Muoio, N.B. Ruderman, M.C. Haigis (2013) SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell 50, 686-98.

 

48) M. Lakshminarasimhan, U. Curth, S. Moniot, S. Mosalaganti, S. Raunser, C. Steegborn (2013) Molecular architecture of the human protein deacetylase Sirt1 and its regulation by AROS and resveratrol. Biosci. Rep. 33:e00037.

 

47) M. Lakshminarasimhan, D. Rauh, M. Schutkowski, C. Steegborn (2013) Sirt1 activation by resveratrol is substrate sequence-selective. Aging 5, 151-4.

 

46) S. Moniot, M. Schutkowski, C. Steegborn (2013) Crystal structure analysis of human Sirt2 and its ADP-ribose complex. J. Struct. Biol. 182, 136-43.

 

45) B. Suenkel, F. Fischer, C. Steegborn (2013) Inhibition of the human deacylase Sirtuin 5 by the indole GW5074. Bioorg. Med. Chem. Lett. 23, 143-6.

 

44) Gertz M, Nguyen GT, Fischer F, Suenkel B, Schlicker C, Fränzel B, Tomaschewski J, Aladini F, Becker C, Wolters D, Steegborn C. (2012) A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One 7:e49761.

 

43) Fischer F, Gertz M, Suenkel B, Lakshminarasimhan M, Schutkowski M, Steegborn C. (2012) Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition. PLoS One 7:e45098.

 

42) S. Middelhaufe, M. Leipelt, L.R. Levin, J. Buck, C. Steegborn (2012) Identification of a haem domain in human soluble adenylate cyclase. Biosci. Rep. 32, 491-9.

 

41) H. Topal, N.B. Fulcher, J. Bitterman, E. Salazar, J. Buck, L.R Levin, M.J Cann, MC Wolfgang, C. Steegborn (2012). Crystal Structure and Regulation Mechanisms of the CyaB Adenylyl Cyclase from the Human Pathogen Pseudomonas aeruginosa. J. Mol. Biol. 416, 271-86.

 

40) C. Schlicker, G. Boanca, M. Lakshminarasimhan, C. Steegborn (2011). Structure-based development of novel sirtuin inhibitors. Aging 3, 852-72.

 

39) R. Acin-Perez, M. Russwurm, K. Günnewig, M. Gertz, G. Zoidl, L. Ramos, J. Buck, L.R. Levin, J. Rassow, G. Manfredi, C. Steegborn (2011). A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration. J. Biol. Chem. 286, 30423-32.

 

38) M. Russwurm, C. Schlicker, M. Weyand, D. Koesling, C. Steegborn (2011). Crystal structure of the GAF-B domain from human phosphodiesterase 5. Proteins 79, 1682-1687.

 

37) A. Hall, L. De Sordi, D.M. MacCallum, H. Topal, R. Eaton, J.W. Bloor, G.K. Robinson, L.R. Levin, J. Buck, Y. Wang, N.A.R. Gow, C. Steegborn, F.A. Mühlschlegel (2010). CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans. PLoS Pathogens 6:e1001193.

                                     

36) A. Innocenti, R.A. Hall, C. Schlicker, A. Scozzafava, C. Steegborn, F.A. Mühlschlegel, C.T. Supuran (2009) Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides. Bioorg. Med. Chem. 17, 4503-4509.

 

35) M. Gertz, F. Fischer, M. Leipelt, D. Wolters, C. Steegborn (2009) Identification of Peroxiredoxin 1 as a novel interaction partner for the lifespan regulator protein p66Shc. Aging 1, 254-265.

 

34) C. Schlicker, R.A. Hall, D. Vullo, S. Middelhaufe, M. Gertz, C.T. Supuran, F.A. Mühlschlegel, C. Steegborn (2009) Structure and inhibition of the CO2-sensing carbonic anhydrase Can2 from the pathogenic fungus Cryptococcus neoformans. J. Mol. Biol. 385, 1207-1220.

 

33) A. Rauch, M. Leipelt, M. Russwurm, C. Steegborn (2008) Crystal structure of the guanylyl cyclase Cya2. Proc. Natl. Acad. Sci. USA 105, 15720-15725.

 

32) A. Innocenti, F.A. Mühlschlegel, R.A. Hall, C. Steegborn, A. Scozzafava, C.T. Supuran (2008) Carbonic anhydrase inhibitors. Inhibition of the beta-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions. Bioorg. Med. Chem. Lett. 18, 5066-5070.

 

31) M. Tammenkoski, K. Koivula, E. Cusanelli, M. Zollo, C. Steegborn, A.A. Baykov, R. Lahti (2008) The human metastasis regulator protein h-prune is a short-chain exopolyphosphatase. Biochemistry 47, 9707-9713.

 

30) C. Schlicker, M. Gertz, D. Papatheodorou, B. Kachholz, C.F.W. Becker, C. Steegborn (2008) Substrates and regulation mechanisms for the human mitochondrial Sirtuins Sirt3 and Sirt5. J. Mol Biol. 382, 790-801.

 

29) C. Schlicker, A. Rauch, K.C. Hess, B. Kachholz, L.R. Levin, J. Buck, C. Steegborn (2008) Structure-based development of novel adenylyl cyclase inhibitors. J. Med. Chem. 51, 4456-4464.

 

28) M. Gertz, F. Fischer, D. Wolters, C. Steegborn (2008) Activation of the life-span regulator p66Shc through reversible disulfide bond formation. Proc. Natl Acad. Sci. USA 105, 5705-5709.

 

27) L. Garzia, A. D’Angelo, A. Amoresano, S.K. Knauer, C. Cirulli, C. Campanella, R.H. Stauber, C. Steegborn, A. Iolascon, M. Zollo (2007) Phosphorylation of nm23H1 by CKI induces complex formation with h-prune and promotes cell motility. Oncogene 27, 1853-1864.

 

26) S. Middelhaufe, L. Garzia, U.-M. Ohndorf, B. Kachholz, M. Zollo, C. Steegborn (2007) Domain mapping on the human metastasis regulator protein h-Prune reveals a C-terminal dimerization domain. Biochem. J. 407, 199-205.

 

25) H.G. Mannherz, E. Ballweber, M. Galla, S. Villard, C. Granier, C. Steegborn, A. Schmidtmann, K. Jaquet, B. Pope, A.G.M. Weeds (2007) Mapping the ADF/Cofilin Binding Site on Monomeric Actin by Competitive Cross-linking and Peptide Array: Evidence for a Second Binding Site on Monomeric Actin. J. Mol. Biol. 366, 745-755.

 

24) E.G. Mogensen, G. Janbon, J. Chaloupka, C. Steegborn, M. Shun Fu, F. Moyrand, T. Klengel, D. S. Pearson, M. A. Geeves, J. Buck, L. R. Levin, and F. A. Mühlschlegel (2006) CO2 sensing in Cryptococcus neoformans involves the carbonic anhydrase Can2. Eukaryot. Cell 5, 103-111.

                                     

23) C. Steegborn, T.N. Litvin, K.C. Hess, A.B. Capper, R. Taussig, J. Buck, L.R. Levin, H. Wu (2005) A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen. J. Biol. Chem. 280, 31754 - 31759.

 

22) C. Steegborn, T.N. Litvin, L.R. Levin, J. Buck, H. Wu (2005) Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment. Nature Struct. Mol. Biol. 12, 32-37.

 

21) H. Ye, T.-S. Chen, X. Xu, M. Pennycooke, H. Wu, C. Steegborn (2004) Crystal structure of the putative adapter protein MTH1859. J. Struct. Biol. 148, 251-256.

 

20) G. Xu, R.L. Rich, C. Steegborn, T. Min, Y. Huang, D.G. Myszka, H. Wu (2003) Mutational analyses of the p35/caspase Interaction. A bowstring kinetic model of caspase inhibition by p35. J. Biol. Chem. 278, 5455-61.

 

19) M.A. Augustin, A.S. Reichert, H. Betat, R. Huber, M. Moerl, C. Steegborn (2003) Crystal Structure of the human CCA-adding enzyme: Insights into template-independent polymerization. J. Mol. Biol. 328, 985-994.

 

18) A. Messerschmidt, M. Worbs, C. Steegborn, M.C. Wahl, R. Huber, B. Laber, T. Clausen (2003) What determines enzymatic specificity in the cys-met-metabolism PLP-dependent enzyme family: Crystal structure of cystathionine g-lyase from yeast and intrafamiliar structural comparison. Biol. Chem. 384, 373-386.

 

17) S.P. Stabler, C. Steegborn, M.C. Wahl, J. Oliveriusova, J.P. Kraus, R.H. Allen, C. Wagner, S.H. Mudd (2002) Elevated plasma total homocysteine in severe MAT I/III deficiency. Metabolism 51, 981-988.

 

16) W. Rossoll, A.-K. Kroening, U.-M. Ohndorf, C. Steegborn, S. Jablonka, M. Sendtner (2002) Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons? Hum. Mol. Genet. 11, 93-105.

 

15) C. Steegborn, O. Danot, R. Huber, T. Clausen (2001) Crystal structure of transcription factor MalT domain III: A novel helix repeat fold implicated in regulated oligomerisation. Structure 9, 1051-1060.

 

14) C. Steegborn, B. Laber, A. Messerschmidt, R. Huber, T. Clausen (2001) Crystal structures of cystathionine g-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor. J. Mol. Biol. 311, 789-801.

 

13) U.-M. Ohndorf, C. Steegborn, R. Knijff, P. Sondermann (2001) Contributions of the individual domains in human La protein to its RNA 3’-end binding activity. J. Biol. Chem. 276, 27188-27196.

 

12) A. Dorowski, A. Hofmann, C. Steegborn, M. Bociu, R. Huber (2001) Crystal structure of paprika ferredoxin-NADP+ reductase. Implications for the electron transfer pathway. J. Biol. Chem. 276, 9253-9263.

 

11) C. Steegborn, H. Schneider-Hassloff, M. Zeeb, J. Balbach (2000) Cooperativity of a protein folding reaction probed at multiple chain positions by real-time 2D NMR spectroscopy. Biochemistry 39, 7910-7919.

 

10) T. Clausen, J. Kaiser, C. Steegborn, R. Huber, D. Kessler (2000) Crystal structure of the cystine C-S lyase from Synechocystis: stabilization of cysteine persulfide for FeS cluster biosynthesis. Proc. Natl Acad. Sci. USA 97, 3856-3861.

 

9) T. Clausen, A. Schlegel, R. Peist, E. Schneider, C. Steegborn, Y.-S. Chang, A. Haase, G.P. Bourenkov, H.D. Bartunik, W. Boos (2000) X-ray structure of MalY from Escherichia coli: a pyridoxal 5’-phosphate-dependent enzyme acting as a modulator in mal gene expression. EMBO J. 19, 831-842.

 

8) V. Schreiber, C. Steegborn, T. Clausen, W. Boos, E. Richet (1999) A new mechanism for the control of a prokaryotic transcriptional regulator: antagonistic binding of positive and negative effectors. Mol. Microbiol. 35, 765-776.

 

7) T. Clausen, M.C. Wahl, A. Messerschmidt, R. Huber, J. Fuhrmann, B. Laber, W. Streber, C. Steegborn (1999) Cloning, purification and characterisation of cystathionine g-synthase from Nicotiana tabacum. Biol. Chem. 380, 1237-1242.

 

6) C. Steegborn, A. Messerschmidt, B. Laber, W. Streber, R. Huber, T. Clausen (1999) The crystal structure of cystathionine g-synthase from Nicotiana tabacum reveals its substrate and reaction specificity. J. Mol. Biol. 290, 983-996.

 

5) C. Steegborn, T. Clausen, P. Sondermann, U. Jacob, M. Worbs, S. Marinkovic, R. Huber, M.C. Wahl (1999) Kinetics and inhibition of recombinant human cystathionine g-lyase - Toward the rational control of transsulfuration. J. Biol. Chem. 274, 12675-12684.

 

4) J. Balbach, C. Steegborn, T. Schindler, F.X. Schmid (1999) A protein folding intermediate of ribonuclease T1 characterized at high resolution by 1D and 2D real-time NMR spectroscopy. J. Mol. Biol. 285, 829-842.

 

3) C. Steegborn, P. Skladal (1997) Construction and characterization of the direct piezoelectric immunosensor for atrazine operating in solution. Biosens. Bioelectron. 12, 19-27.

 

2) A.U. Metzger, T. Schindler, D. Willbold, M. Kraft, C. Steegborn, A. Volkmann, R.W. Frank, P. Roesch (1996) Structural rearrangements on HIV-1 Tat (32-72) TAR complex formation. FEBS Lett. 384, 255-259.

 

1) M. Sprinzl, C. Steegborn, F. Huebel, S. Steinberg (1996) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 24, 68-72.

 

 

Reviews & Editorials      

22) Balbach M, Fushimi M, Huggins DJ, Steegborn C, Meinke PT, Levin LR, Buck J. (2020) Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration. Biol Reprod, 103(2):176-182 <PubMed>

21) Tomaselli D, Steegborn C, Mai A, Rotili D.(2020) Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer. Front Oncol. 2020<PubMed>

20) C.M. Palmeira, J.S. Teodoro, J.A. Amorim, C. Steegborn, D.A. Sinclair, A.P. Rolo (2019). Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins. Free Radic Biol Med. 141, 483-491.

 

19) Steegborn C, Schweizer U. (2019) Structure and Mechanism of Iodothyronine Deiodinases - What We Know, What We Don't Know, and What Would Be Nice to Know. Exp Clin Endocrinol Diabetes,128,6-7.  <PubMed>

 

18) Wiggins SV, Steegborn C, Levin LR, Buck J. (2018) Pharmacological modulation of the CO2/HCO3-/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase. Pharmacol. Ther., 190, 173-186.

 

17) H. Dai, D.A. Sinclair, J.L. Ellis, C. Steegborn (2018) Sirtuin activators and inhibitors: Promises, achievements, and challenges. Pharmacol. Ther. 188, 140-154.

 

16) Steegborn C (2017) JSB Paper-of-the Year Award: “Sébastien Moniot et al. (2013) Crystal structure analysis of human Sirt2 and its ADP-ribose complex. J. Struct. Biol. 182, 136–43”. J. Struct. Biol. 198, 1-2.

 

15) U. Schweizer, H. Towell, A. Vit, A. Rodriguez-Ruiz, C. Steegborn (2017) Structural aspects of thyroid hormone binding to proteins and competitive interactions with natural and synthetic compounds. Mol. Cell. Endocrinol. 55, R37-52.

 

14) M. Gertz, C. Steegborn (2016) Using mitochondrial sirtuins as drug targets: disease implications and available compounds. Cell. Mol. Life Sci. 73, 2871-9.

 

13) B. Suenkel, C. Steegborn (2016) Recombinant preparation, biochemical analysis, and structure determination of Sirtuin family histone/protein deacylases. Methods in Enzymology, Vol. Enzymes of Epigenetics 573, 183-208.

 

12) Klionsky DJ, Abdelmohsen K, et al., C. Steegborn, et al. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1-222.

 

11) U. Schweizer, C. Steegborn (2015) New insights into the structure and mechanism of iodothyronine deiodinases. J. Mol. Endocrinol. 55, R37-52.

 

10) C. Steegborn (2014) Structure, mechanism, and regulation of soluble adenylyl cyclases – similarities and differences to transmembrane adenylyl cyclases. Biochim. Biophys. Acta - Molecular Basis of Disease 1842, 2535-47.

 

9) M. Schutkowski, F. Fischer, C. Roessler, C. Steegborn (2014) New assays and approaches for discovery and design of Sirtuin modulators. Expert Opin. Drug Discov. 9, 183-99.

 

8) S. Moniot, M. Weyand, C. Steegborn (2012). Structures, substrates, and regulators of Mammalian sirtuins - opportunities and challenges for drug development. Front. Pharmacol. 3:16.

 

7) M. Lakshminarasimhan, C. Steegborn (2011) Emerging mitochondrial signaling mechanisms in physiology, aging processes, and as drug targets. Exp. Gerontol. 46, 174-7.

 

6) M. Gertz, C. Steegborn (2010) The mitochondrial apoptosis pathway and p66Shc--a regulatory redox enzyme or an adapter protein snuggling around? Cell Cycle 9, 4425-6.

 

5)   J.A. Baur, D. Chen, E.N. Chini, K. Chua, H.Y. Cohen, R. de Cabo, C. Deng, S. Dimmeler, D. Gius, L.P. Guarente, S.L. Helfand, S. Imai, H. Itoh, T. Kadowaki, D. Koya, C. Leeuwenburgh, M. McBurney, Y. Nabeshima, C. Neri, P. Oberdoerffer, R.G. Pestell, B. Rogina, J. Sadoshima, V. Sartorelli, M. Serrano, D.A. Sinclair, C. Steegborn, M. Tatar, H.A. Tissenbaum, Q. Tong, K. Tsubota, A. Vaquero, E. Verdin (2010) Dietary restriction: standing up for sirtuins. Science 329, 1012-3.

4) M. Gertz M, C. Steegborn (2010) The lifespan-regulator p66Shc in mitochondria - redox enzyme or redox sensor? Antioxid. Redox Signal. 13, 1417-28.

3) M. Gertz, C. Steegborn (2010) Function and regulation of the mitochondrial Sirtuin isoform Sirt5 in mammalia. Biochim. Biophys. Acta 1804, 1658-65.

2) M. Kamenetsky, S. Middelhaufe, E.M. Bank, L.R. Levin, J. Buck, C. Steegborn (2006) Molecular details of cAMP generation in mammalian cells: a tale of two systems. J. Mol. Biol. 362, 623-639.

1) C. Steegborn, T. Clausen (2000) Toward specific inhibition of the pyridoxal-5’-phosphate dependent transsulfuration enzymes. Recent Res. Dev. Biochem. 2, 191-207.

 

 

Book chapters

S. Moniot, W. You, C. Steegborn (2018) Structural and mechanistic insights in Sirtuin catalysis and pharmacological modulation. In “Introductory Review on Sirtuins in Biology and Disease” Eds. L. Guarente, R. Mostoslavsky, A. Kazantsev

U.-M. Ohndorf, C. Schlicker, C. Steegborn (2009) Crystallographic studies on carbonic anhydrases from fungal pathogens for structure-assisted drug development. In “Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications” Eds. C.T. Supuran, J.-Y. Winum.

 

 

Patent applications 

C. Steegborn, R. Huber, T. Clausen, A. Messerschmidt, et al. (1999) Inhibitoren der pflanzlichen Cystathionin gamma-Synthase. German Patent Application 199 535 19.1

Buck, L.R. Levin. L. Ramos-Espiritu, C. Steegborn (2017) Inhibitors of soluble adenylyl cyclase. US patent application 62/328,806

 

 

 


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