High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

PLoS ONE

Volumn 5, Issue 11, 2010, Pages

  Niesen, Frank H ^a   Schultz, Lena ^b   Jadhav, Ajit ^b   Bhatia, Chitra ^a   Guo, Kunde ^a   Maloney, David J ^b   Pilka, Ewa S ^a   Wang, Minghua ^a   Oppermann, Udo ^b,c   Heightman, Tom D ^a   Simeonov, Anton ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

15 HYDROXYPROSTAGLANDIN DEHYDROGENASE; 15 HYDROXYPROSTAGLANDIN DEHYDROGENASE INHIBITOR; ENZYME INHIBITOR; UNCLASSIFIED DRUG; 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE; NICOTINAMIDE ADENINE DINUCLEOTIDE; PROSTAGLANDIN E2;

ARTICLE; COMPUTER MODEL; CONCENTRATION RESPONSE; CROSS REACTION; DRUG BINDING; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; MOLECULAR CLONING; MOLECULAR DOCKING; PROTEIN EXPRESSION; PROTEIN PURIFICATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; BINDING COMPETITION; BINDING SITE; BIOCATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; ENZYME SPECIFICITY; KINETICS; METABOLISM; OXIDATION REDUCTION REACTION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; X RAY CRYSTALLOGRAPHY;

BINDING SITES; BINDING, COMPETITIVE; BIOCATALYSIS; CRYSTALLOGRAPHY, X-RAY; DINOPROSTONE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HUMANS; HYDROXYPROSTAGLANDIN DEHYDROGENASES; KINETICS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NAD; OXIDATION-REDUCTION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 78249266924     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0013719     Document Type: Article

References (58)

1. Samuelsson B (2000) The discovery of the leukotrienes. Am J Respir Crit Care Med 161: S2-6.
2. Samuelsson B (1986) Leukotrienes and other lipoxygenase products. Prog Lipid Res 25: 13-18.
3. Samuelsson B (1983) From studies of biochemical mechanism to novel biological mediators: prostaglandin endoperoxides, thromboxanes, and leukotrienes. Nobel Lecture, 8 December 1982. Biosci Rep 3: 791-813.
4. Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58: 362-366.
5. Wang D, Dubois RN (2006) Prostaglandins and cancer. Gut 55: 115-122.
6. Tai HH, Tong M, Ding Y (2007) 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer. Prostaglandins Other Lipid Mediat 83: 203-208.
7. Dubinett SM, Mao JT, Hazra S (2008) Focusing downstream in lung cancer prevention: 15-hydroxyprostaglandin dehydrogenase. Cancer Prev Res (Phila Pa) 1: 223-225.
8. Yoshimatsu K, Altorki NK, Golijanin D, Zhang F, Jakobsson PJ, et al. (2001) Inducible prostaglandin E synthase is overexpressed in non-small cell lung cancer. Clin Cancer Res 7: 2669-2674.
9. Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jakobsson PJ, et al. (2001) Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res 7: 3971-3976.
10. Cohen EG, Almahmeed T, Du B, Golijanin D, Boyle JO, et al. (2003) Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma. Clin Cancer Res 9: 3425-3430.
11. Buczynski MW, Dumlao DS, Dennis EA (2009) Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology. J Lipid Res 50: 1015-1038.
12. FitzGerald GA (2003) COX-2 and beyond: Approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2: 879-890.
13. Kim EH, Surh YJ (2008) The role of 15-deoxy-delta(12,14)-prostaglandin J(2), an endogenous ligand of peroxisome proliferator-activated receptor gamma, in tumor angiogenesis. Biochem Pharmacol 76: 1544-1553.
14. Rizzo G, Fiorucci S (2006) PPARs and other nuclear receptors in inflammation. Curr Opin Pharmacol 6: 421-427.
15. Tai HH, Ensor CM, Tong M, Zhou H, Yan F (2002) Prostaglandin catabolizing enzymes. Prostaglandins Other Lipid Mediat 68-69: 483-493.
16. Wermuth B, Bohren KM, Heinemann G, von Wartburg JP, Gabbay KH (1988) Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein. J Biol Chem 263: 16185-16188.
17. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, et al. (2009) The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative. Chem Biol Interact 178: 94-98.
18. Kavanagh KL, Jornvall H, Persson B, Oppermann U (2008) Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol Life Sci 65: 3895-3906.
19. Krook M, Marekov L, Jornvall H (1990) Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. Biochemistry 29: 738-743.
20. Ensor CM, Yang JY, Okita RT, Tai HH (1990) Cloning and sequence analysis of the cDNA for human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. J Biol Chem 265: 14888-14891.
21. Ensor CM, Tai HH (1994) Bacterial expression and site-directed mutagenesis of two critical residues (tyrosine-151 and lysine-155) of human placental NAD(+)- dependent 15-hydroxyprostaglandin dehydrogenase. Biochim Biophys Acta 1208: 151-156.
22. Cho H, Tai HH (2002) Inhibition of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by cyclooxygenase inhibitors and chemopreventive agents. Prostaglandins Leukot Essent Fatty Acids 67: 461-465.
23. Cho H, Tai HH (2002) Thiazolidinediones as a novel class of NAD(+)- dependent 15-hydroxyprostaglandin dehydrogenase inhibitors. Arch Biochem Biophys 405: 247-251.
24. Berry CN, Hoult JR, Peers SH, Agback H (1983) Inhibition of prostaglandin 15- hydroxydehydrogenase by sulphasalazine and a novel series of potent analogues. Biochem Pharmacol 32: 2863-2871.
25. Zhang JH, Chung TD, Oldenburg KR (1999) A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen 4: 67-73.
26. Eastwood BJ, Farmen MW, Iversen PW, Craft TJ, Smallwood JK, et al. (2006) The minimum significant ratio: a statistical parameter to characterize the reproducibility of potency estimates from concentration-response assays and estimation by replicate-experiment studies. J Biomol Screen 11: 253-261.
27. Jadhav A, Ferreira RS, Klumpp C, Mott BT, Austin CP, et al. (2010) Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J Med Chem 53: 37-51.
28. Simeonov A, Jadhav A, Thomas CJ, Wang Y, Huang R, et al. (2008) Fluorescence spectroscopic profiling of compound libraries. J Med Chem 51: 2363-2371.
29. Yasgar A, Shinn P, Jadhav A, Auld D, Michael S, et al. (2008) Compound Management for Quantitative High-Throughput Screening. JALA Charlottesv Va 13: 79-89.
30. Niesen FH, Berglund H, Vedadi M (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2: 2212-2221.
31. Filling C, Berndt KD, Benach J, Knapp S, Prozorovski T, et al. (2002) Critical residues for structure and catalysis in short-chain dehydrogenases/reductases. J Biol Chem 277: 25677-25684.
32. Kroe RR, Regan J, Proto A, Peet GW, Roy T, et al. (2003) Thermal denaturation: a method to rank slow binding, high-affinity P38alpha MAP kinase inhibitors. J Med Chem 46: 4669-4675.
33. Lo MC, Aulabaugh A, Jin G, Cowling R, Bard J, et al. (2004) Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery. Anal Biochem 332: 153-159.
34. Fedorov O, Niesen FH, Knapp S (in press) Kinase Inhibitor Selectivity Profiling using Differential Scanning Fluorimetry (DSF). Methods Biotechnol.
35. Zhou H, Yan F, Tai HH (2001) C-Terminal region of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase is involved in the interaction with prostaglandin substrates. Eur J Biochem 268: 3368-3374.
36. Cho H, Hamza A, Zhan CG, Tai HH (2005) Key NAD+-binding residues in human 15-hydroxyprostaglandin dehydrogenase. Arch Biochem Biophys 433: 447-453.
37. Segel IH (1993) Enzyme Kinetics - Behaviour and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. New York: Wiley Interscience.
38. Cer RZ, Mudunuri U, Stephens R, Lebeda FJ (2009) IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding. Nucleic Acids Res 37: W441-445.
39. de Kok PM, Beijer NA, Buck HM, Sluyterman LA, Meijer EM (1988) Molecular mechanics calculation of geometries of NAD+ derivatives, modified in the nicotinamide group, in a ternary complex with horse liver alcohol dehydrogenase. Eur J Biochem 175: 581-585.
40. Jornvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, et al. (1995) Short-chain dehydrogenases/reductases (SDR). Biochemistry 34: 6003-6013.
41. Oppermann U, Filling C, Hult M, Shafqat N, Wu X, et al. (2003) Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem Biol Interact 143-144: 247-253.
42. Kallberg Y, Oppermann U, Jornvall H, Persson B (2002) Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes. Protein Sci 11: 636-641.
43. Rudolph FB (1979) Product inhibition and abortive complex formation. Methods Enzymol 63: 411-436.
44. Tong M, Tai HH (2000) Induction of NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase expression by androgens in human prostate cancer cells. Biochem Biophys Res Commun 276: 77-81.
45. Michael S, Auld D, Klumpp C, Jadhav A, Zheng W, et al. (2008) A robotic platform for quantitative high-throughput screening. Assay Drug Dev Technol 6: 637-657.
46. Inglese J, Auld DS, Jadhav A, Johnson RL, Simeonov A, et al. (2006) Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A 103: 11473-11478.
47. Hill AV (1910) The possible effect of the aggregation of the molecules of hemoglobin. J Physiol 40: IV-VIII.
48. Leslie AG (2006) The integration of macromolecular diffraction data. Acta Crystallogr D Biol Crystallogr 62: 48-57.
49. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50: 760-763.
50. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, et al. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658-674.
51. Ito K, Nakajima Y, Ichihara E, Ogawa K, Katayama N, et al. (2006) D-3- hydroxybutyrate dehydrogenase from Pseudomonas fragi: molecular cloning of the enzyme gene and crystal structure of the enzyme. J Mol Biol 355: 722-733.
52. Sogabe S, Yoshizumi A, Fukami TA, Shiratori Y, Shimizu S, et al. (2003) The crystal structure and stereospecificity of levodione reductase from Corynebacterium aquaticum M-13. J Biol Chem 278: 19387-19395.
53. Schlieben NH, Niefind K, Muller J, Riebel B, Hummel W, et al. (2005) Atomic resolution structures of R-specific alcohol dehydrogenase from Lactobacillus brevis provide the structural bases of its substrate and cosubstrate specificity. J Mol Biol 349: 801-813.
54. Morris RJ, Perrakis A, Lamzin VS (2002) ARP/wARP's model-building algorithms. I. The main chain. Acta Crystallogr D Biol Crystallogr 58: 968-975.
55. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
56. Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53: 240-255.
57. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47: 1739-1749.
58. Jorgensen WL, Tiradorives J (1988) The Opls Potential Functions for Proteins - Energy Minimizations for Crystals of Cyclic-Peptides and Crambin. Journal of the American Chemical Society 110: 1657-1666.