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Intrinsic thermodynamics of high affinity inhibitor binding to recombinant human carbonic anhydrase IV

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Abstract

Membrane-associated carbonic anhydrase (CA) isoform IV participates in carbon metabolism and pH homeostasis and is implicated in the development of eye diseases such as retinitis pigmentosa and glaucoma. A series of substituted benzenesulfonamides were designed and their binding affinity to CA IV was determined by fluorescent thermal shift assay and isothermal titration calorimetry (ITC). Compound [(4-chloro-2-phenylsulfanyl-5-sulfamoyl-benzoyl)amino]propyl acetate (19) bound CA IV with the K d of 1.0 nM and exhibited significant selectivity over the remaining 11 human CA isoforms. The compound could be developed as a drug targeting CA IV. Various forms of recombinant CA IV were produced in Escherichia coli and mammalian cell cultures. Comparison of their temperature stability in various buffers and salt solutions demonstrated that CA IV is most stable at slightly alkaline conditions and at elevated sodium sulfate concentrations. High-resolution X-ray crystallographic structures of ortho-Cl and meta-thiazole-substituted benzene sulfonamide in complex with CA IV revealed the position of and interactions between the ligand and the protein. Sulfonamide inhibitor binding to CA IV is linked to several reactions—the deprotonation of the sulfonamide amino group, the protonation of CA–Zn(II)-bound hydroxide at the active site of CA IV, and the compensating reactions of the buffer. The dissection of binding-linked reactions yielded the intrinsic thermodynamic parameters, characterizing the interaction between CA IV and the sulfonamides in the binding-able protonation forms, including Gibbs energy, enthalpy, and entropy, that could be used for the characterization of binding to any CA in the process of drug design.

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Abbreviations

AZM:

Acetazolamide (also abbreviated as AAZ, ACTAZ)

BSA:

Benzenesulfonamide

CA:

Carbonic anhydrase

CA IV:

Isozyme 4 of the human carbonic anhydrase protein family

EZA:

Ethoxzolamide

FTSA:

Fluorescent thermal shift assay

ITC:

Isothermal titration calorimetry

MZM:

Methazolamide (also METHZ)

PAMBS:

Para-aminomethyl-benzenesulfonamide

TFS:

Trifluoromethane sulfonamide (also TFMSA)

TPM:

Topiramate

References

  • Alterio V, Fiore AD, D’Ambrosio K, Supuran CT, Simone GD (2012) Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 112:4421–4468

    Article  CAS  PubMed  Google Scholar 

  • Baird JTT, Waheed A, Okuyama T, Sly WS, Fierke CA (1997) Catalysis and inhibition of human carbonic anhydrase IV. Biochemistry 36:2669–2678

    Article  CAS  PubMed  Google Scholar 

  • Balaydin HT, Senturk M, Menzek A (2012) Synthesis and carbonic anhydrase inhibitory properties of novel cyclohexanonyl bromophenol derivatives. Bioorg Med Chem Lett 22:1352–1357

    Article  CAS  PubMed  Google Scholar 

  • Barker H, Aaltonen M, Pan P, Vähätupa M, Kaipiainen P, May U, Prince S, Uusitalo-Järvinen H, Waheed A, Pastoreková S, Sly WS, Parkkila S, Järvinen TA (2017) Role of carbonic anhydrases in skin wound healing. Exp Mol Med 49:e334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brandts JF, Lin LN (1990) Study of strong to ultratight protein interactions using differential scanning calorimetry. Biochemistry 29:6927–6940

    Article  CAS  PubMed  Google Scholar 

  • Breton S (2001) The cellular physiology of carbonic anhydrases. JOP 2:159–164

    CAS  PubMed  Google Scholar 

  • Cammer W, Zhang H, Tansey F (1995) Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse. J Neurosci Res 40:451–457

    Article  CAS  PubMed  Google Scholar 

  • Čapkauskaitė E, Zubrienė A, Smirnov A, Torresan J, Kišonaitė M, Kazokaitė J, Gylytė J, Michailovienė V, Jogaitė V, Manakova E, Gražulis S, Tumkevičius S, Matulis D (2013) Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII. Bioorg Med Chem 21:6937–6947

    Article  PubMed  Google Scholar 

  • Christie KN, Thomson C, Xue L, Lucocq JM, Hopwood D (1997) Carbonic anhydrase isoenzymes I, II, III, and IV are present in human esophageal epithelium. J Histochem Cytochem 45:35–40

    Article  CAS  PubMed  Google Scholar 

  • Cimmperman P, Baranauskienė L, Jachimovičiūtė S, Jachno J, Torresan J, Michailovienė V, Matulienė J, Sereikaitė J, Bumelis V, Matulis D (2008) A quantitative model of thermal stabilization and destabilization of proteins by ligands. Biophys J 95:3222–3231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collaborative Computational Project, N. 4 (1994) The CCP4 suite: programs for protein crystallography. Acta Cryst D 50:760–763

    Article  Google Scholar 

  • Datta R, Waheed A, Bonapace G, Shah GN, Sly WS (2009) Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV. Proc Natl Acad Sci USA 106:3437–3442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Datta R, Shah GN, Rubbelke TS, Waheed A, Rauchman M, Goodman AG, Katze MG, Sly WS (2010) Progressive renal injury from transgenic expression of human carbonic anhydrase IV folding mutants is enhanced by deficiency of p58IPK. Proc Natl Acad Sci USA 107:6448–6452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Del Prete S, Vullo D, Fisher GM, Andrews KT, Poulsen S-A, Capasso C, Supuran CT (2014) Discovery of a new family of carbonic anhydrases in the malaria pathogen Plasmodium falciparum—the η-carbonic anhydrases. Bioorg Med Chem Lett 24:4389–4396

    Article  PubMed  Google Scholar 

  • Dudutiene V, Matuliene J, Smirnov A, Timm DD, Zubriene A, Baranauskiene L, Morkunaite V, Smirnoviene J, Michailoviene V, Juozapaitiene V et al (2014) Discovery and characterization of novel selective inhibitors of carbonic anhydrase IX. J Med Chem 57:9435–9446

    Article  CAS  PubMed  Google Scholar 

  • Dudutienė V, Zubrienė A, Smirnov A, Gylytė J, Timm D, Manakova E, Gražulis S, Matulis D (2013) 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem 21:2093–2106

    Article  PubMed  Google Scholar 

  • Dudutienė V, Zubrienė A, Smirnov A, Timm DD, Smirnovienė J, Kazokaitė J, Michailovienė V, Zakšauskas A, Manakova E, Gražulis S, Matulis D (2015) Functionalization of fluorinated benzenesulfonamides and their inhibitory properties toward carbonic anhydrases. ChemMedChem 10:662–687

    Article  PubMed  Google Scholar 

  • Elleuche S, Pöggeler S (2010) Carbonic anhydrases in fungi. Microbiology 156:23–29

    Article  CAS  PubMed  Google Scholar 

  • Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D 60:2126–2132

    Article  PubMed  Google Scholar 

  • Ferrari S, Di Iorio E, Barbaro V, Ponzin D, Sorrentino FS, Parmeggiani F (2011) Retinitis pigmentosa: genes and disease mechanisms. Curr Genomics 12:238–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferry JG (2010) The gamma class of carbonic anhydrases. Biochim Biophys Acta 1804:374–381

    Article  CAS  PubMed  Google Scholar 

  • Fujikura T, Miigata K, Hashimoto S, Imai K, Takenaka T (1982) Studies on benzenesulfonamide derivatives with alpha- and beta-adrenergic antagonistic and antihypertensive activities. Chem Pharm Bull 30:4092–4101

    Article  CAS  PubMed  Google Scholar 

  • Goldberg RMRN, Lennen Kishore N (2002) Thermodynamic quantities for the ionization reactions of buffers. J Phys Chem Ref Data 31:231–370

    Article  CAS  Google Scholar 

  • Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Innocenti A, Villar R, Martinez-Merino V, Gil MJ, Scozzafava A, Vullo D, Supuran CT (2005) Carbonic anhydrase inhibitors: inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with benzo[b]thiophene 1,1-dioxide sulfonamides. Bioorg Med Chem Lett 15:4872–4876

    Article  CAS  PubMed  Google Scholar 

  • Jogaitė V, Zubrienė A, Michailovienė V, Gylytė J, Morkūnaitė V, Matulis D (2013) Characterization of human carbonic anhydrase XII stability and inhibitor binding. Bioorg Med Chem 21:1431–1436

    Article  PubMed  Google Scholar 

  • Kikutani S, Nakajima K, Nagasato C, Tsuji Y, Miyatake A, Matsuda Y (2016) Thylakoid luminal θ-carbonic anhydrase critical for growth and photosynthesis in the marine diatom Phaeodactylum tricornutum. Proc Natl Acad Sci USA 113:9828–9833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kišonaitė M, Zubrienė A, Čapkauskaitė E, Alexey S, Smirnovienė Joana V, Kairys V, Michailovienė E, Manakova S Gražulis, Matulis D (2014) Intrinsic thermodynamics and structure correlation of benzenesulfonamides with a pyrimidine moiety binding to carbonic anhydrases I, II, VII, XII, and XIII. PLoS ONE 9:e114106

    Article  PubMed  PubMed Central  Google Scholar 

  • Kivelä A-J, Kivelä J, Saarnio J, Parkkila S (2005) Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumours. World J Gastroenterol 11:155–163

    Article  PubMed  PubMed Central  Google Scholar 

  • Köhn L, Burstedt MSI, Jonsson F, Kadzhaev K, Haamer E, Sandgren O, Golovleva I (2008) Carrier of R14 W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1. Invest Ophthalmol Vis Sci 49:3172–3177

    Article  PubMed  Google Scholar 

  • Krishnamurthy VM, Kaufman GK, Urbach AR, Gitlin I, Gudiksen KL, Weibel DB, Whitesides GM (2008) Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Chem Rev 108:946–1051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372:774–797

    Article  CAS  PubMed  Google Scholar 

  • Lane TW, Saito MA, George GN, Pickering IJ, Prince RC, Morel FMM (2005) Biochemistry: a cadmium enzyme from a marine diatom. Nature 435:42

    Article  CAS  PubMed  Google Scholar 

  • Leslie AGW (2006) The integration of macromolecular diffraction data. Acta Crystallogr D 62:48–57

    Article  PubMed  Google Scholar 

  • Linkuviene V, Matuliene J, Juozapaitiene V, Michailoviene V, Jachno J, Matulis D (2016) Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX. Biochim Biophys Acta 1860:708–718

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Bu W, Xi J, Mortazavi SR, Cheung-Lau JC, Dmochowski IJ, Loll PJ (2012) Beyond the detergent effect: a binding site for sodium dodecyl sulfate (SDS) in mammalian apoferritin. Acta Crystallogr D 68:497–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maryanoff BE, Costanzo MJ, Nortey SO, Greco MN, Shank RP, Schupsky JJ, Ortegon MP, Vaught JL (1998) Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives. J Med Chem 41:1315–1343

    Article  CAS  PubMed  Google Scholar 

  • Matulis D, Lovrien R (1998) 1-Anilino-8-naphthalene sulfonate anion-protein binding depends primarily on ion pair formation. Biophys J 74:422–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matulis D, Todd MJ (2004) Thermodynamics-structure correlations of sulfonamide inhibitor binding to carbonic anhydrase. In: Ladbury JE, Doyle ML (eds) Biocalorimetry 2. Wiley, Chichester, pp 107–132

    Google Scholar 

  • Matulis D, Baumann CG, Bloomfield VA, Lovrien RE (1999) 1-anilino-8-naphthalene sulfonate as a protein conformational tightening agent. Biopolymers 49:451–458

    Article  CAS  PubMed  Google Scholar 

  • Matulis D, Kranz JK, Salemme FR, Todd MJ (2005) Thermodynamic stability of carbonic anhydrase: measurements of binding affinity and stoichiometry using ThermoFluor. Biochemistry 44:5258–5266

    Article  CAS  PubMed  Google Scholar 

  • McMurtrie HL, Cleary HJ, Alvarez BV, Loiselle FB, Sterling D, Morgan PE, Johnson DE, Casey JR (2004) The bicarbonate transport metabolon. J Enzyme Inhib Med Chem 19:231–236

    Article  CAS  PubMed  Google Scholar 

  • Morris AL, MacArthur MW, Hutchinson EG, Thornton JM (1992) Stereochemical quality of protein structure coordinates. Proteins 12:345–364

    Article  CAS  PubMed  Google Scholar 

  • Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D 53:240–255

    Article  CAS  PubMed  Google Scholar 

  • Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT (2005) Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett 15:3828–3833

    Article  CAS  PubMed  Google Scholar 

  • Oelschlager H (1961) 3-Alkyl-6-Halogen-Aniline Aus p-Halogenierten Fettaromatischen Ketonen. Justus Liebigs Ann Chem 641:81–94

    Article  CAS  Google Scholar 

  • Otwinowski Z, Minor W (1997) Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol 276:307–326

    Article  CAS  Google Scholar 

  • Pastorekova S, Parkkila S, Pastorek J, Supuran CT (2004) Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J Enzyme Inhib Med Chem 19:199–229

    Article  CAS  PubMed  Google Scholar 

  • Purkerson JM, Schwartz GJ (2007) The role of carbonic anhydrases in renal physiology. Kidney Int 71:103–115

    Article  CAS  PubMed  Google Scholar 

  • Slavik J, Horak J, Rihova L, Kotyk A (1982) Anilinonaphthalene sulfonate fluorescence and amino acid transport in yeast. J Membr Biol 64:175–179

    Article  CAS  PubMed  Google Scholar 

  • Stams T, Christianson DW (2000) X-ray crystallographic studies of mammalian carbonic anhydrase isozymes. Birkhäuser, Basel, pp 159–174

    Google Scholar 

  • Stams T, Nair SK, Okuyama T, Waheed A, Sly WS, Christianson DW (1996) Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-Å resolution. Proc Natl Acad Sci USA 93:13589–13594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sterling D, Alvarez BV, Casey JR (2002) The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV. J Biol Chem 277:25239–25246

    Article  CAS  PubMed  Google Scholar 

  • Stryer L (1965) The interaction of a naphthalene dye with apomyoglobin and apohemoglobin. A fluorescent probe of non-polar binding sites. J Mol Biol 13:482–495

    Article  CAS  PubMed  Google Scholar 

  • Supuran CT (2008) Carbonic anhydrases—an overview. Curr Pharm Des 14:603–614

    Article  CAS  PubMed  Google Scholar 

  • Supuran CT (2004) Carbonic anhydrases: catalytic and inhibition mechanisms, distribution and physiological roles. In: Supuran CT, Scozzafawa A, Conway J (eds) Carbonic anhydrase–its inhibitors and activators. CRC Press, Boca Raton, pp 1–24

    Google Scholar 

  • Svichar N, Waheed A, Sly WS, Hennings JC, Hübner CA, Chesler M (2009) Carbonic anhydrases CA4 and CA14 both enhance AE3-mediated Cl–HCO3- exchange in hippocampal neurons. J Neurosci 29:3252–3258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamai S, Waheed A, Cody LB, Sly WS (1996) Gly-63–>Gln substitution adjacent to His-64 in rodent carbonic anhydrase IVs largely explains their reduced activity. Proc Natl Acad Sci USA 93:13647–13652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vagin A, Teplyakov A (1997) MOLREP: an automated program for molecular replacement. J Appl Cryst 30:1022–1025

    Article  CAS  Google Scholar 

  • Vernier W, Chong W, Rewolinski D, Greasley S, Pauly T, Shaw M, Dinh D, Ferre RA, Nukui S, Ornelas M, Reyner E (2010) Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation. Bioorg Med Chem 18:3307–3319

    Article  CAS  PubMed  Google Scholar 

  • Waheed A, Okuyama T, Heyduk T, Sly WS (1996) Carbonic anhydrase IV: purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds. Arch Biochem Biophys 333:432–438

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Horton JR, Maunus R, Wilson GG, Roberts RJ, Cheng X (2005) Structure of HinP1I endonuclease reveals a striking similarity to the monomeric restriction enzyme MspI. Nucleic Acids Res 33:1892–1901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Tsoi H, Li X, Wang H, Gao J, Wang K, Go MY, Ng SC, Chan FK, Sung JJ, Yu J (2016) Carbonic anhydrase IV inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP-WT1-TBL1 axis. Gut 65:1482–1493

    Article  CAS  PubMed  Google Scholar 

  • Zolfaghari Emameh R, Barker HR, Syrjänen L, Urbański L, Supuran CT, Parkkila S (2016a) Identification and inhibition of carbonic anhydrases from nematodes. J Enzyme Inhib Med Chem 31:176–184

    Article  CAS  PubMed  Google Scholar 

  • Zolfaghari Emameh R, Barker HR, Tolvanen MEE, Parkkila S, Hytönen VP (2016b) Horizontal transfer of β-carbonic anhydrase genes from prokaryotes to protozoans, insects, and nematodes. Parasit Vectors 9:152

    Article  PubMed  PubMed Central  Google Scholar 

  • Zubrienė A, Čapkauskaitė E, Gylytė J, Kišonaitė M, Tumkevičius S, Matulis D (2014) Benzenesulfonamides with benzimidazole moieties as inhibitors of carbonic anhydrases I, II, VII, XII and XIII. J Enzyme Inhib Med Chem 29:124–131

    Article  PubMed  Google Scholar 

  • Zubrienė A, Smirnovienė J, Smirnov A, Morkūnaitė V, Michailovienė V, Jachno J, Juozapaitienė V, Norvaišas P, Manakova E, Gražulis S, Matulis D (2015) Intrinsic thermodynamics of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamide binding to carbonic anhydrases by isothermal titration calorimetry. Biophys Chem 205:51–65

    Article  PubMed  Google Scholar 

  • Zubrienė A, Smirnov A, Dudutienė V, Timm DD, Matulienė J, Michailovienė V, Zakšauskas A, Manakova E, Gražulis S, Matulis D (2017) Intrinsic thermodynamics and structures of 2,4- and 3,4-substituted fluorinated benzenesulfonamides binding to carbonic anhydrases. ChemMedChem 12:161–176

    Article  PubMed  Google Scholar 

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Acknowledgements

This research was funded by the Grant SEN-04/2015 from the Research Council of Lithuania to J.M. and by National Institutes of Health Grants HL049413 and HL073813 to E.D.C. The authors also acknowledge the COST projects CM1406, CM1407, CA15126, and CA15135. The authors are grateful to Gleb Burenkov for assistance with data collection at EMBL P14 beamline at the PETRA III storage ring, DESY Hamburg. The authors also thank Tracey Baird for editorial assistance in the preparation of this manuscript.

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  1. Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, 10257, Vilnius, Lithuania

    Aurelija Mickevičiūtė, David D. Timm, Marius Gedgaudas, Vaida Linkuvienė, Vilma Michailovienė, Asta Zubrienė, Alexey Smirnov, Edita Čapkauskaitė, Lina Baranauskienė, Jelena Jachno, Jurgita Revuckienė, Jurgita Matulienė & Daumantas Matulis

  2. Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA

    Zhiwei Chen, Abdul Waheed, Enrico Di Cera & William S. Sly

  3. Department of Protein-DNA Interactions, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, 10257, Vilnius, Lithuania

    Elena Manakova & Saulius Gražulis

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  1. Aurelija Mickevičiūtė
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Mickevičiūtė, A., Timm, D.D., Gedgaudas, M. et al. Intrinsic thermodynamics of high affinity inhibitor binding to recombinant human carbonic anhydrase IV. Eur Biophys J 47, 271–290 (2018). https://doi.org/10.1007/s00249-017-1256-0

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