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Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam.

Poulos TL, Howard AJ
Biochemistry 26 8165-74 (1987)
Related entries: 1phd, 1phf, 1phg

Cited: 98 times
EuropePMC logo PMID: 3442650

Abstract

The crystal structures of metyrapone- and 1-, 2-, and 4-phenylimidazole-inhibited complexes of cytochrome P-450cam have been refined to a nominal resolution of 2.1 A and compared with the 1.63-A camphor-bound structure. With the exception of 2-phenylimidazole, each of the inhibitors forms an N-Fe bond with the heme iron atom while part of the inhibitor sits in the camphor-binding pocket. In the 2-phenylimidazole complex, a water molecule or hydroxide ion coordinates with the heme iron atom while the inhibitor binds in the camphor pocket adjacent to the aqua ligand. Each of the inhibitors forces the central region of helix I that forms part of the O2 binding pocket to move away from the inhibitor, with the exception of 2-phenylimidazole where the helix moves in toward the inhibitor. In addition, the Tyr-96 region, which provides specific contact points with the substrate, is perturbed, although to varying degrees with each inhibitor. These perturbations include large, localized changes in Debye-Waller or temperature factors, indicative of changes in dynamical fluctuations. The largest inhibitor, metyrapone, causes the fewest changes, while 2-phenylimidazole binding causes the largest, especially in helix I. The large 2-phenylimidazole-induced movement of helix I can be rationalized on the basis of the inhibitor imidazole group's hydrogen-bonding requirements.

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  1. PDB ligand conformational energies calculated quantum-mechanically. Sitzmann M, Weidlich IE, Filippov IV, Liao C, Peach ML, Ihlenfeldt WD, Karki RG, Borodina YV, Cachau RE, Nicklaus MC. J Chem Inf Model 52 739-756 (2012)
  2. Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d and CYP125A1. Conner KP, Cruce AA, Krzyaniak MD, Schimpf AM, Frank DJ, Frank DJ, Ortiz de Montellano P, Atkins WM, Bowman MK. Biochemistry 54 1198-1207 (2015)
  3. Rational design of an orthogonal noncovalent interaction system at the MUPP1 PDZ11 complex interface with CaMKIIα-derived peptides in human fertilization. Zhang YL, Han ZF. Mol Biosyst 13 2145-2151 (2017)


Reviews citing this publication (19)

  1. Implications of protein flexibility for drug discovery. Teague SJ. Nat Rev Drug Discov 2 527-541 (2003)
  2. Clinical and molecular pharmacology of etomidate. Forman SA. Anesthesiology 114 695-707 (2011)
  3. Diversity of P450 enzymes in the biosynthesis of natural products. Podust LM, Sherman DH. Nat Prod Rep 29 1251-1266 (2012)
  4. Suicide inactivation of peroxidases and the challenge of engineering more robust enzymes. Valderrama B, Ayala M, Vazquez-Duhalt R. Chem Biol 9 555-565 (2002)
  5. Comparative aspects of the mammalian cytochrome P450 IV gene family. Gibson GG. Xenobiotica 19 1123-1148 (1989)
  6. Conformational plasticity and structure/function relationships in cytochromes P450. Pochapsky TC, Kazanis S, Dang M. Antioxid Redox Signal 13 1273-1296 (2010)
  7. Structural properties of peroxidases. Banci L. J Biotechnol 53 253-263 (1997)
  8. Allosteric phenomena in cytochrome P450-catalyzed monooxygenations. Hlavica P, Lewis DF. Eur J Biochem 268 4817-4832 (2001)
  9. Interactions of cytochrome P450s with their ligands. Conner KP, Woods CM, Atkins WM. Arch Biochem Biophys 507 56-65 (2011)
  10. New cytochrome P450 mechanisms: implications for understanding molecular basis for drug toxicity at the level of the cytochrome. Shakunthala N. Expert Opin Drug Metab Toxicol 6 1-15 (2010)
  11. Cytochromes P450: their active-site structure and mechanism of oxidation. Koymans L, Donné-op den Kelder GM, Koppele Te JM, Vermeulen NP. Drug Metab Rev 25 325-387 (1993)
  12. Trapping interactions between catalytic domains and carrier proteins of modular biosynthetic enzymes with chemical probes. Gulick AM, Aldrich CC. Nat Prod Rep 35 1156-1184 (2018)
  13. Quantitative structure-activity relationships (QSAR) and molecular modelling in cancer research. Kubinyi H. J Cancer Res Clin Oncol 116 529-537 (1990)
  14. The Hypothalamic-Pituitary-Adrenal Axis and Anesthetics: A Review. Besnier E, Clavier T, Compere V. Anesth Analg 124 1181-1189 (2017)
  15. Modeling the active sites of cytochrome P450s and glutathione S-transferases, two of the most important biotransformation enzymes. De Groot MJ, Vermeulen NP. Drug Metab Rev 29 747-799 (1997)
  16. Computational methods for the design of potent aromatase inhibitors. Favia AD, Nicolotti O, Stefanachi A, Leonetti F, Carotti A. Expert Opin Drug Discov 8 395-409 (2013)
  17. Identifying and characterizing promiscuous targets: implications for virtual screening. Pérez-Nueno VI, Ritchie DW. Expert Opin Drug Discov 7 1-17 (2012)
  18. Mechanisms of inhibition of xenobiotic-metabolizing enzymes. Testa B. Xenobiotica 20 1129-1137 (1990)
  19. [The key and the lock. I. The basis of drug action]. Kubinyi H. Pharm Unserer Zeit 23 158-168 (1994)

Articles citing this publication (76)

  1. Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Hasemann CA, Kurumbail RG, Boddupalli SS, Peterson JA, Deisenhofer J. Structure 3 41-62 (1995)
  2. GEMDOCK: a generic evolutionary method for molecular docking. Yang JM, Chen CC. Proteins 55 288-304 (2004)
  3. Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution. Hasemann CA, Ravichandran KG, Peterson JA, Deisenhofer J. J Mol Biol 236 1169-1185 (1994)
  4. Conformational energy penalties of protein-bound ligands. Boström J, Norrby PO, Liljefors T. J Comput Aided Mol Des 12 383-396 (1998)
  5. EADock: docking of small molecules into protein active sites with a multiobjective evolutionary optimization. Grosdidier A, Zoete V, Michielin O. Proteins 67 1010-1025 (2007)
  6. Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv. McLean KJ, Carroll P, Lewis DG, Dunford AJ, Seward HE, Neeli R, Cheesman MR, Marsollier L, Douglas P, Smith WE, Rosenkrands I, Cole ST, Leys D, Parish T, Munro AW. J Biol Chem 283 33406-33416 (2008)
  7. Thermophilic cytochrome P450 (CYP119) from Sulfolobus solfataricus: high resolution structure and functional properties. Park SY, Yamane K, Adachi S, Shiro Y, Weiss KE, Maves SA, Sligar SG. J Inorg Biochem 91 491-501 (2002)
  8. The structure of the cytochrome p450cam-putidaredoxin complex determined by paramagnetic NMR spectroscopy and crystallography. Hiruma Y, Hass MA, Kikui Y, Liu WM, Ölmez B, Skinner SP, Blok A, Kloosterman A, Koteishi H, Löhr F, Schwalbe H, Nojiri M, Ubbink M. J Mol Biol 425 4353-4365 (2013)
  9. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Mast N, White MA, Bjorkhem I, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA. Proc Natl Acad Sci U S A 105 9546-9551 (2008)
  10. Substrate-, hormone-, and cAMP-regulated cytochrome P450 degradation. Eliasson E, Johansson I, Ingelman-Sundberg M. Proc Natl Acad Sci U S A 87 3225-3229 (1990)
  11. Putidaredoxin reductase-putidaredoxin-cytochrome p450cam triple fusion protein. Construction of a self-sufficient Escherichia coli catalytic system. Sibbesen O, De Voss JJ, Montellano PR. J Biol Chem 271 22462-22469 (1996)
  12. Molecular cloning and sequence analysis of cDNA encoding rat adrenal cytochrome P-450(11)beta. Nonaka Y, Matsukawa N, Morohashi, Omura T, Ogihara T, Teraoka H, Okamoto M. FEBS Lett 255 21-26 (1989)
  13. Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam: a molecular dynamics study. Helms V, Wade RC. Biophys J 69 810-824 (1995)
  14. Molecular modelling of CYP3A4 from an alignment with CYP102: identification of key interactions between putative active site residues and CYP3A-specific chemicals. Lewis DF, Eddershaw PJ, Goldfarb PS, Tarbit MH. Xenobiotica 26 1067-1086 (1996)
  15. Pharmacologic stimulation of cytochrome P450 46A1 and cerebral cholesterol turnover in mice. Mast N, Li Y, Linger M, Clark M, Wiseman J, Pikuleva IA. J Biol Chem 289 3529-3538 (2014)
  16. A 175-psec molecular dynamics simulation of camphor-bound cytochrome P-450cam. Paulsen MD, Ornstein RL. Proteins 11 184-204 (1991)
  17. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain. Mast N, Charvet C, Pikuleva IA, Stout CD. J Biol Chem 285 31783-31795 (2010)
  18. Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins. Kirton SB, Murray CW, Verdonk ML, Taylor RD. Proteins 58 836-844 (2005)
  19. Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis: conformational flexibility and histidine ligation state. Xu LH, Fushinobu S, Ikeda H, Wakagi T, Shoun H. J Bacteriol 191 1211-1219 (2009)
  20. A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS. Ishida N, Aoyama Y, Hatanaka R, Oyama Y, Imajo S, Ishiguro M, Oshima T, Nakazato H, Noguchi T, Maitra US. Biochem Biophys Res Commun 155 317-323 (1988)
  21. Development of quantitative structure-binding affinity relationship models based on novel geometrical chemical descriptors of the protein-ligand interfaces. Zhang S, Golbraikh A, Tropsha A. J Med Chem 49 2713-2724 (2006)
  22. The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro and in vivo. Shafaati M, Mast N, Beck O, Nayef R, Heo GY, Björkhem-Bergman L, Lütjohann D, Björkhem I, Björkhem I, Pikuleva IA. J Lipid Res 51 318-323 (2010)
  23. Three clusters of conformational states in p450cam reveal a multistep pathway for closing of the substrate access channel. Lee YT, Glazer EC, Wilson RF, Stout CD, Goodin DB. Biochemistry 50 693-703 (2011)
  24. Structural and thermodynamic consequences of 1-(4-chlorophenyl)imidazole binding to cytochrome P450 2B4. Zhao Y, Sun L, Muralidhara BK, Kumar S, White MA, Stout CD, Halpert JR. Biochemistry 46 11559-11567 (2007)
  25. 3D-QSAR methods on the basis of ligand-receptor complexes. Application of COMBINE and GRID/GOLPE methodologies to a series of CYP1A2 ligands. Lozano JJ, Pastor M, Cruciani G, Gaedt K, Centeno NB, Gago F, Sanz F. J Comput Aided Mol Des 14 341-353 (2000)
  26. Antagonistic effects of hydrostatic pressure and osmotic pressure on cytochrome P-450cam spin transition. Di Primo C, Deprez E, Hoa GH, Douzou P. Biophys J 68 2056-2061 (1995)
  27. Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics. Roumen L, Sanders MP, Pieterse K, Hilbers PA, Plate R, Custers E, de Gooyer M, Smits JF, Beugels I, Emmen J, Ottenheijm HC, Leysen D, Hermans JJ. J Comput Aided Mol Des 21 455-471 (2007)
  28. Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2. Belkina NV, Lisurek M, Ivanov AS, Bernhardt R. J Inorg Biochem 87 197-207 (2001)
  29. Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome P450cam and chloroperoxidase. Schünemann V, Jung C, Terner J, Trautwein AX, Weiss R. J Inorg Biochem 91 586-596 (2002)
  30. Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response. Mast N, Zheng W, Stout CD, Pikuleva IA. J Biol Chem 288 4613-4624 (2013)
  31. Intermediates in the reaction of substrate-free cytochrome P450cam with peroxy acetic acid. Schünemann V, Jung C, Trautwein AX, Mandon D, Weiss R. FEBS Lett 479 149-154 (2000)
  32. Method for comparing the structures of protein ligand-binding sites and application for predicting protein-drug interactions. Minai R, Matsuo Y, Onuki H, Hirota H. Proteins 72 367-381 (2008)
  33. On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data. Lewi PJ, de Jonge M, Daeyaert F, Koymans L, Vinkers M, Heeres J, Janssen PA, Arnold E, Das K, Clark AD, Hughes SH, Boyer PL, de Béthune MP, Pauwels R, Andries K, Kukla M, Ludovici D, De Corte B, Kavash R, Ho C. J Comput Aided Mol Des 17 129-134 (2003)
  34. Autocatalytic nitration of P450CAM by peroxynitrite. Daiber A, Schöneich C, Schmidt P, Jung C, Ullrich V. J Inorg Biochem 81 213-220 (2000)
  35. Comparison of Antifungal Azole Interactions with Adult Cytochrome P450 3A4 versus Neonatal Cytochrome P450 3A7. Godamudunage MP, Grech AM, Scott EE. Drug Metab Dispos 46 1329-1337 (2018)
  36. Ethylbenzene hydroxylation by cytochrome P450cam. Filipovic D, Paulsen MD, Loida PJ, Sligar SG, Ornstein RL. Biochem Biophys Res Commun 189 488-495 (1992)
  37. Theoretical and experimental evaluation of a CYP106A2 low homology model and production of mutants with changed activity and selectivity of hydroxylation. Lisurek M, Simgen B, Antes I, Bernhardt R. Chembiochem 9 1439-1449 (2008)
  38. Cloning and expression of a member of a new cytochrome P-450 family: cytochrome P-450lin (CYP111) from Pseudomonas incognita. Ropp JD, Gunsalus IC, Sligar SG. J Bacteriol 175 6028-6037 (1993)
  39. Allosteric transitions in cytochrome P450eryF explored with pressure-perturbation spectroscopy, lifetime FRET, and a novel fluorescent substrate, Fluorol-7GA. Davydov DR, Davydova NY, Halpert JR. Biochemistry 47 11348-11359 (2008)
  40. Analysis of active site motions from a 175 picosecond molecular dynamics simulation of camphor-bound cytochrome P450cam. Paulsen MD, Bass MB, Ornstein RL. J Biomol Struct Dyn 9 187-203 (1991)
  41. Conformational dynamics in cytochrome P450-substrate interactions. Li H, Poulos TL. Biochimie 78 695-699 (1996)
  42. Heme-pocket-hydration change during the inactivation of cytochrome P-450camphor by hydrostatic pressure. Di Primo C, Hui Bon Hoa G, Douzou P, Sligar SG. Eur J Biochem 209 583-588 (1992)
  43. Reverse type I inhibitor of Mycobacterium tuberculosis CYP125A1. Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM. Bioorg Med Chem Lett 21 332-337 (2011)
  44. Dual binding mode of "bitter sugars" to their human bitter taste receptor target. Fierro F, Giorgetti A, Carloni P, Meyerhof W, Alfonso-Prieto M. Sci Rep 9 8437 (2019)
  45. Specific and non-specific effects of potassium cations on substrate-protein interactions in cytochromes P450cam and P450lin. Deprez E, Gill E, Helms V, Wade RC, Hui Bon Hoa G. J Inorg Biochem 91 597-606 (2002)
  46. Solvation of the active site of cytochrome P450-cam. Wade RC. J Comput Aided Mol Des 4 199-204 (1990)
  47. Three-dimensional modelling of human cytochrome P450 1A2 and its interaction with caffeine and MeIQ. Lozano JJ, López-de-Briñas E, Centeno NB, Guigó R, Sanz F. J Comput Aided Mol Des 11 395-408 (1997)
  48. Effects of monovalent cations on cytochrome P-450 camphor. Evidence for preferential binding of potassium. Deprez E, Di Primo C, Hoa GH, Douzou P. FEBS Lett 347 207-210 (1994)
  49. Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102. Lewis DF, Lake BG. Xenobiotica 29 763-781 (1999)
  50. Reliable Target Prediction of Bioactive Molecules Based on Chemical Similarity Without Employing Statistical Methods. Forouzesh A, Samadi Foroushani S, Forouzesh F, Zand E. Front Pharmacol 10 835 (2019)
  51. Substrate mobility in a deeply buried active site: analysis of norcamphor bound to cytochrome P-450cam as determined by a 201-psec molecular dynamics simulation. Bass MB, Paulsen MD, Ornstein RL. Proteins 13 26-37 (1992)
  52. Experimental resolution of the free energies of aqueous solvation contributions to ligand-protein binding: quinone-QA site interactions in the photosynthetic reaction center protein. Warncke K, Dutton PL. Proc Natl Acad Sci U S A 90 2920-2924 (1993)
  53. Models of the bis-histidine-coordinated ferricytochromes: Mössbauer and EPR spectroscopic studies of low-spin iron(III) tetrapyrroles of various electronic ground states and axial ligand orientations. Benda R, Schünemann V, Trautwein AX, Cai S, Reddy Polam J, Watson CT, Shokhireva TKh, Walker FA. J Biol Inorg Chem 8 787-801 (2003)
  54. Multicopy molecular dynamics simulations suggest how to reconcile crystallographic and product formation data for camphor enantiomers bound to cytochrome P-450cam. Das B, Helms V, Lounnas V, Wade RC. J Inorg Biochem 81 121-131 (2000)
  55. Using molecular dynamics to probe the structural basis for enhanced stability in thermal stable cytochromes P450. Meharenna YT, Poulos TL. Biochemistry 49 6680-6686 (2010)
  56. Cloning, sequencing, and characterization of CYP1A1 cDNA from leaping mullet (Liza Saliens) liver and implications for the potential functions of its conserved amino acids. Sen A, Hu C, Urbach E, Wang-Buhler J, Yang Y, Arinc E, Buhler DR. J Biochem Mol Toxicol 15 243-255 (2001)
  57. Interactions of substrate and product with cytochrome P450: P4502B4 versus P450cam. Narasimhulu S, Havran LM, Axelsen PH, Winkler JD. Arch Biochem Biophys 353 228-238 (1998)
  58. Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model. Besnier E, Clavier T, Tonon MC, Selim J, Lefevre-Scelles A, Morin F, Tamion F, Dureuil B, Castel H, Compere V. Anesthesiology 127 347-354 (2017)
  59. Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors. Kavanagh ME, Gray JL, Gilbert SH, Coyne AG, McLean KJ, Davis HJ, Munro AW, Abell C. ChemMedChem 11 1924-1935 (2016)
  60. Comparative 1-substituted imidazole inhibition of cytochrome p450 isozyme-selective activities in human and mouse hepatic microsomes. Franklin MR, Constance JE. Drug Metab Rev 39 309-322 (2007)
  61. Enantioselective Benzylic Hydroxylation Catalysed by P450 Monooxygenases: Characterisation of a P450cam Mutant Library and Molecular Modelling. Eichler A, Gricman Ł, Herter S, Kelly PP, Turner NJ, Pleiss J, Flitsch SL. Chembiochem 17 426-432 (2016)
  62. Roles of two surface residues near the access channel in the substrate recognition by cytochrome P450cam. Behera RK, Mazumdar S. Biophys Chem 135 1-6 (2008)
  63. Spectroelectrochemistry of cytochrome P450cam. Bistolas N, Christenson A, Ruzgas T, Jung C, Scheller FW, Wollenberger U. Biochem Biophys Res Commun 314 810-816 (2004)
  64. Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate. Yeh HC, Gerfen GJ, Wang JS, Tsai AL, Wang LH. Biochemistry 48 917-928 (2009)
  65. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions. Kelly PP, Eichler A, Herter S, Kranz DC, Turner NJ, Flitsch SL. Beilstein J Org Chem 11 1713-1720 (2015)
  66. CW EPR parameters reveal cytochrome P450 ligand binding modes. Lockart MM, Rodriguez CA, Atkins WM, Bowman MK. J Inorg Biochem 183 157-164 (2018)
  67. Effect of Mutation and Substrate Binding on the Stability of Cytochrome P450BM3 Variants. Geronimo I, Denning CA, Rogers WE, Othman T, Huxford T, Heidary DK, Glazer EC, Payne CM. Biochemistry 55 3594-3606 (2016)
  68. Metal-Free meta-Selective Alkyne Oxyarylation with Pyridine N-Oxides: Rapid Assembly of Metyrapone Analogues. Chen X, Ruider SA, Hartmann RW, González L, Maulide N. Angew Chem Int Ed Engl 55 15424-15428 (2016)
  69. NMR studies of recombinant cytochrome P450cam mutants. Wakasugi K, Ishimori K, Morishima I. Biochimie 78 763-770 (1996)
  70. The Effects of Single-Dose Etomidate Versus Propofol on Cortisol Levels in Pediatric Patients Undergoing Urologic Surgery: A Randomized Controlled Trial. Du Y, Chen YJ, He B, Wang YW. Anesth Analg 121 1580-1585 (2015)
  71. Ab initio molecular modeling in the study of drug metabolism. Segall MD, Payne MC, Ellis SW, Tucker GT, Boyes RN. Eur J Drug Metab Pharmacokinet 22 283-289 (1997)
  72. Enantioselectivity of some 1-[(benzofuran-2-yl) phenylmethyl] imidazoles as aromatase (P450AROM) inhibitors. Khodarahmi GA, Laughton CA, Smith HJ, Nicholls PJ. J Enzyme Inhib 16 401-416 (2001)
  73. Interplanar torsion in the S1<--S0 electronic spectrum of jet cooled 1-phenylimidazole. Robertson EG, Thompson CD, Morrison RJ. J Chem Phys 121 12421-12427 (2004)
  74. Heterobifunctional photoaffinity probes for cytochrome P450 2B. Antonovic L, Hodek P, Smrcek S, Novák P, Sulc M, Strobel HW. Arch Biochem Biophys 370 208-215 (1999)
  75. Multiple drug binding modes in Mycobacterium tuberculosis CYP51B1. Lockart MM, Butler JT, Mize CJ, Fair MN, Cruce AA, Conner KP, Atkins WM, Bowman MK. J Inorg Biochem 205 110994 (2020)
  76. Photoaffinity labeling of P450Cam by an imidazole-tethered benzophenone probe. Trnka MJ, Doneanu CE, Trager WF. Arch Biochem Biophys 445 95-107 (2006)


Related citations provided by authors (2)

  1. Inhibitor-Induced Conformational Change in Cytochrome P450-Cam. Raag R, Li H, Jones BC, Poulos TL Biochemistry 32 4571- (1993)
  2. Crystal Structure of Substrate-Free Pseudomonas Putida Cytochrome P450. Poulos TL, Finzel BC, Howard AJ Biochemistry 25 5314- (1986)

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