Comparison of crystal structures of human type 3 3α-hydroxysteroid dehydrogenase reveals an "induced-fit" mechanism and a conserved basic motif involved in the binding of androgen

Protein Science

Volumn 14, Issue 6, 2005, Pages 1485-1497

  Couture, Jean François ^a,b   De Jésus Tran, Karine Pereira ^a   Roy, Anne Marie ^a   Cantin, Line ^a   Côté, Pierre Luc ^a   Legrand, Pierre ^a,c   Luu The, Van ^a   Labrie, Fernand ^a   Breton, Rock ^a  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c SYNCHROTRON SOLEIL   (France)

Author keywords

Aldo keto reductase; Crystal structure; Hydroxysteroid dehydrogenase; Induced fit mechanism

Indexed keywords

ACETIC ACID; ALDEHYDE REDUCTASE; ANDROGEN; ARGININE; CITRIC ACID; HYDROXYSTEROID DEHYDROGENASE; INDANONE DERIVATIVE; POLYCYCLIC AROMATIC HYDROCARBON; STEROID; TESTOSTERONE;

ARTICLE; BINDING SITE; COMPLEX FORMATION; CONFORMATION; CRYSTAL STRUCTURE; ENZYME ACTIVITY; ENZYME BINDING; ENZYME SUBSTRATE COMPLEX; HORMONE BINDING; HORMONE STRUCTURE; MOLECULE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN MOTIF;

3-ALPHA-HYDROXYSTEROID DEHYDROGENASE (B-SPECIFIC); AMINO ACID MOTIFS; ANDROGENS; CRYSTALLOGRAPHY, X-RAY; HUMANS; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

EID: 22444449692     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1110/ps.051353205     Document Type: Article

References (48)

1. Barski, O.A., Gabbay, K.H., and Bohren, K.M. 1996. The C-terminal loop of aldehyde reductase determines the substrate and inhibitor specificity. Biochemistry 35: 14276-14280.
2. Bennett, M.J., Schlegel, B.P., Jez, J.M., Penning, T.M., and Lewis, M. 1996. Structure of 3 α-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry 35: 10702-10711.
3. Bennett, M.J., Albert, R.H., Jez, J.M., Ma, H., Penning, T.M., and Lewis, M. 1997. Steroid recognition and regulation of hormone action: Crystal structure of testosterone and NADP+ bound to 3 α-hydroxysteroid/ dihydrodiol dehydrogenase. Structure 5: 799-812.
4. Brunger, A.T., Adams, P.D., Clore, G.M., Delano, W.L., Gros, P., Grosse-Kunstleve, R.W., Jiang, J.-S., Kuszewski, J., Nilges, M., Pannu, N.S., et al. 1998. Crystallography & NMR system: A new software system for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54: 905-921.
5. Burczynski, M.E., Harvey, R.G., and Penning, T.M. 1998. Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: Oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione. Biochemistry 37: 6781-6790.
6. Burczynski, M.E., Sridhar, G.R., Palackal, N.T., and Penning, T.M. 2001. The reactive oxygen species- and Michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene. J. Biol. Chem. 276: 2890-2897.
7. Chakravarty, S., Bhinge, A., and Varadarajan, R. 2002. A procedure for detection and quantitation of cavity volumes proteins. Application to measure the strength of the hydrophobic driving force in protein folding. J. Biol. Chem. 277: 31345-31353.
8. Couture, J.F., Cantin, L., Legrand, P., Luu-The, V., Labrie, F., and Breton, R. 2002. Expression, crystallization and preliminary X-ray analysis of human and rabbit 20α-hydroxysteroid dehydrogenases in complex with NADP(H) and various steroid substrates. Acta Crystallogr. D Biol. Crystallogr. 58: 135-139.
9. Couture, J.F., Legrand, P., Cantin, L., Luu-The, V., Labrie, F., and Breton, R. 2003. Human 20α-hydroxysteroid dehydrogenase: Crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids. J. Mol. Biol. 331: 593-604.
10. Couture, J.F., Legrand, P., Cantin, L., Labrie, F., Luu-The, V., and Breton, R. 2004. Loop relaxation, a mechanismthat explains the reduced specificity of rabbit 20α-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily. J. Mol. Biol. 339: 89-102.
11. DelaFuente, G. and Sols, A. 1970. The kinetics of yeast hexokinase in the light of the induced fit involved in the binding of its sugar substrate. Eur. J. Biochem. 16: 234-239.
12. DelaFuente, G., Lagunas, R., and Sols, A. 1970. Induced fit in yeast hexokinase. Eur. J. Biochem. 16: 226-233.
13. Dufort, I., Soucy, P., Labrie, F., and Luu-The, V. 1996. Molecular cloning of human type 3 3 α-hydroxysteroid dehydrogenase that differs from 20 α-hydroxysteroid dehydrogenase by seven amino acids. Biochem. Biophys. Res. Commun. 228: 474-479.
14. Dufort, I., Rheault, P., Huang, X.F., Soucy, P., and Luu-The, V. 1999. Characteristics of a highly labile human type 5 17β-hydroxysteroid dehydrogenase. Endocrinology 140: 568-574.
15. Dufort, I., Labrie, F., and Luu-The, V. 2001. Human types 1 and 3 3 α-hydroxysteroid dehydrogenases: Differential lability and tissue distribution. J. Clin. Endocrinol. Metab. 86: 841-846.
16. Fenn, T.D., Ringe, D., and Petsko, G.A. 2003. POVScript+: A program for model and data visualization using persistence of vision ray-tracing. J. Appl. Crystallogr. 36: 944-947.
17. Heredia, V.V., Kruger, R.G., and Penning, T.M. 2003. Steroid-binding site residues dictate optimal substrate positioning in rat 3α-hydroxysteroid dehydrogenase (3α-HSD or AKR1C9). Chem. Biol. Interact. 143-144: 393-400.
18. Heredia, V.V., Cooper, W.C., Kruger, R.G., Jin, Y., and Penning, T.M. 2004. Alanine scanning mutagenesis of the testosterone binding site of rat 3α-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step. Biochemistry 43: 5832-5841.
19. Hoog, S.S., Pawlowski, J.E., Alzari, P.M., Penning, T.M., and Lewis, M. 1994. Three-dimensional structure of rat liver 3 α-hydroxysteroid/ dihydrodiol dehydrogenase: A member of the aldo-keto reductase superfamily. Proc. Natl. Acad. Sci. 91: 2517-2521.
20. Jin, Y., Stayrook, S.E., Albert, R.H., Palackal, N.T., Penning, T.M., and Lewis, M. 2001. Crystal structure of human type III 3α-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate. Biochemistry 40: 10161-10168.
21. Jones, T.A., Zou, J.Y., Cowan, S.W., and Kjeldgaard, M. 1991. Improved methods for the building of protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47: 110-119.
22. Kabsch, W. 1993. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Crystallogr. 26: 795-800.
23. Kaplan, W. and Littlejohn, T.G. 2001. Swiss-PDB Viewer (Deep View). Brief Bioinform. 2: 195-197.
24. Kavanagh, K.L., Klimacek, M., Nidetzky, B., and Wilson, D.K. 2002. The structure of apo and holo forms of xylose reductase, a dimeric aldoketo reductase from Candida tenuis. Biochemistry 41: 8785-8795.
25. Khurana, S., Powers, D.B., Anderson, S., and Blaber, M. 1998. Crystal structure of 2,5-diketo-D-gluconic acid reductase A complexed with NADPH at 2.1-A resolution. Proc. Natl. Acad. Sci. 95: 6768-6773.
26. Klebe, G., Kramer, O., and Sotriffer, C. 2004. Strategies for the design of inhibitors of aldose reductase, an enzyme showing pronounced induced-fit adaptations. Cell. Mol. Life Sci. 61: 783-793.
27. Kleywegt, G.J. 1994. Detection, delineation, measurement and display of cavities in macromolecular structures. Acta Crystallogr. D Biol. Crystallogr. 50: 178-185.
28. Kozma, E., Brown, E., Ellis, E.M., and Lapthorn, A.J. 2002. The crystal structure of rat liver AKR7A1. A dimeric member of the aldo-keto reductase superfamily. J. Biol. Chem. 277: 16285-16293.
29. Kraulis, P.J. 1991. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24: 946-950.
30. Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M. 1993. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26: 283-291.
31. Lovering, A.L., Ride, J.P., Bunce, C.M., Desmond, J.C., Cummings, S.M., and White, S.A. 2004. Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res. 64: 1802-1810.
32. Luu-The, V., Zhang, Y., Poirier, D., and Labrie, F. 1995. Characteristics of human types 1, 2 and 3 17β-hydroxysteroid dehydrogen aseactivities: Oxidation/reduction and inhibition. J. Steroid Biochem. Mol. Biol. 55: 581-587.
33. Ma, H. and Penning, T.M. 1999. Conversion of mammalian 3α-hydroxysteroid dehydrogenase to 20α-hydroxysteroid dehydrogenase using loop chimeras: Changing specificity from androgens to progestins. Proc. Natl. Acad. Sci. 96: 11161-11166.
34. Matsuura, K., Deyashiki, Y., Sato, K., Ishida, N., Miwa, G., and Hara, A. 1997. Identification of amino acid residues responsible for differences in substrate specificity and inhibitor sensitivity between two human liver dihydrodiol dehydrogenase isoenzymes by site-directed mutagenesis. Biochem. J. 323 (Pt. 1): 61-64.
35. Matsuura, K., Hara, A., Deyashiki, Y., Iwasa, H., Kume, T., Ishikura, S., Shiraishi, H., and Katagiri, Y. 1998. Roles of the C-terminal domains of human dihydrodiol dehydrogenase isoforms in the binding of substrates and modulators: Probing with chimaeric enzymes. Biochem. J. 336 (Pt 2): 429-436.
36. Mesecar, A.D., Stoddard, B.L., and Koshland Jr., D.E. 1997. Orbital steering in the catalytic power of enzymes: Small structural changes with large catalytic consequences. Science 277: 202-206.
37. Murshudov, G.N., Vagin, A.A., and Dodson, E.J. 1997. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53: 240-255.
38. Nahoum, V., Gangloff, A., Legrand, P., Zhu, D.W., Cantin, L., Zhorov, B.S., Luu-The, V., Labrie, F., Breton, R., and Lin, S.X. 2001. Structure of the human 3α-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution. J. Biol. Chem. 276: 42091-42098.
39. Nahoum, V., Gangloff, A., Shi, R., and Lin, S.X. 2003. How estrogen-specific proteins discriminate estrogens from androgens: A common steroid binding site architecture. FASEB J. 17: 1334-1336.
40. Palackal, N.T., Burczynski, M.E., Harvey, R.G., and Penning, T.M. 2001. The ubiquitous aldehyde reductase (AKR1A1) oxidizes proximate carcinogen trans-dihydrodiols to o-quinones: Potential role in polycyclic aromatic hydrocarbon activation. Biochemistry 40: 10901-10910.
41. Palackal, N.T., Lee, S.H., Harvey, R.G., Blair, I.A., and Penning, T.M. 2002. Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells. J. Biol. Chem. 277: 24799-24808.
42. Penning, T.M., Mukharji, I., Barrows, S., and Talalay, P. 1984. Purification and properties of a 3 α-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs. Biochem. J. 222: 601-611.
43. Penning, T.M., Burczynski, M.E., Jez, J.M., Hung, C.F., Lin, H.K., Ma, H., Moore, M., Palackal, N., and Ratnam, K. 2000. Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: Functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem. J. 351: 67-77.
44. Rees-Milton, K.J., Jia, Z., Green, N.C., Bhatia, M., El-Kabbani, O., and Flynn, T.G. 1998. Aldehyde reductase: The role of C-terminal residues in defining substrate and cofactor specificities. Arch. Biochem. Biophys. 355: 137-144.
45. Rondeau, J.M., Tete-Favier, F., Podjarny, A., Reymann, J.M., Barth, P., Biellmann, J.F., and Moras, D. 1992. Novel NADPH-binding domain revealed by the crystal structure of aldose reductase. Nature 355: 469-472.
46. Schlegel, B.P., Jez, J.M., and Penning, T.M. 1998. Mutagenesis of 3 α-hydroxysteroid dehydrogenase reveals a "push-pull" mechanism for proton transfer in aldo-keto reductases. Biochemistry 37: 3538-3548.
47. Sotriffer, C.A., Kramer, O., and Klebe, G. 2004. Probing flexibility and "induced-fit" phenomena in aldose reductase by comparative crystal structure analysis and molecular dynamics simulations. Proteins 56: 52-66.
48. Zhang, Y., Dufort, I., Rheault, P., and Luu-The, V. 2000. Characterization of a human 20α-hydroxysteroid dehydrogenase. J. Mol. Endocrinol. 25: 221-228.