Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2-oxoglutarate dependent oxygenases

Biochemistry

Volumn 53, Issue 15, 2014, Pages 2483-2493

  Tarhonskaya, Hanna ^a   Szöllössi, Andrea ^a   Leung, Ivanhoe K H ^a   Bush, Jacob T ^a   Henry, Luc ^a,b   Chowdhury, Rasheduzzaman ^a   Iqbal, Aman ^a,c   Claridge, Timothy D W ^a   Schofield, Christopher J ^a   Flashman, Emily ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b EPFL   (Switzerland)

^c Structural Genomics Consortium   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTICS; BIOCHEMISTRY; MASS SPECTROMETRY; SEWAGE TREATMENT PLANTS;

2-OXOGLUTARATE; ACTIVE SITE; BINDING STUDIES; CEPHALOSPORIN ANTIBIOTICS; CRYSTALLOGRAPHIC STUDIES; PING-PONGS; RING EXPANSION; TERNARY COMPLEX;

CATALYSIS;

2 OXOGLUTARATE OXYGENASE; 2 OXOGLUTARIC ACID; ADICILLIN; DEACETOXYCEPHALOSPORIN C SYNTHASE; OXYGENASE; SYNTHETASE; UNCLASSIFIED DRUG; WATER;

ARTICLE; CATALYSIS; COMPLEX FORMATION; CONTROLLED STUDY; ELECTROSPRAY MASS SPECTROMETRY; ENZYME BINDING; ENZYME KINETICS; ENZYME METABOLISM; LIGAND BINDING; PRIORITY JOURNAL; PROTEIN QUATERNARY STRUCTURE; PROTON NUCLEAR MAGNETIC RESONANCE; STEADY STATE;

CATALYSIS; CRYSTALLOGRAPHY, X-RAY; INTRAMOLECULAR TRANSFERASES; KETOGLUTARIC ACIDS; KINETICS; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; OXYGENASES; PENICILLIN-BINDING PROTEINS;

EID: 84899415327     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi500086p     Document Type: Article

References (68)

1. Hausinger, R. P. (2004) Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related Enzymes Crit. Rev. Biochem. Mol. Biol. 39, 21-68
2. Loenarz, C. and Schofield, C. J. (2011) Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases Trends Biochem. Sci. 36, 7-18
3. Clifton, I. J., McDonough, M. A., Ehrismann, D., Kershaw, N. J., Granatino, N., and Schofield, C. J. (2006) Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins J. Inorg. Biochem. 100, 644-669
4. Aik, W., McDonough, M. A., Thalhammer, A., Chowdhury, R., and Schofield, C. J. (2012) Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases Curr. Opin. Struct. Biol. 22, 691-700
5. McDonough, M. A., Loenarz, C., Chowdhury, R., Clifton, I. J., and Schofield, C. J. (2010) Structural studies on human 2-oxoglutarate dependent oxygenases Curr. Opin. Struct. Biol. 20, 659-672
6. Koehntop, K., Emerson, J., and Que, L., Jr. (2005) The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes J. Biol. Inorg. Chem. 10, 87-93
7. Bollinger, J. M., Price, J. C., Hoffart, L. M., Barr, E. W., and Krebs, C. (2005) Mechanism of taurine α-ketoglutarate dioxygenase (TauD) from Escherichia coli Eur. J. Inorg. Chem. 2005, 4245-4254
8. Bollinger, J. M., Jr. and Krebs, C. (2007) Enzymatic C-H activation by metal-superoxo intermediates Curr. Opin. Chem. Biol. 11, 151-158
9. Solomon, E. I., Brunold, T. C., Davis, M. I., Kemsley, J. N., Lee, S.-K., Lehnert, N., Neese, F., Skulan, A. J., Yang, Y.-S., and Zhou, J. (1999) Geometric and Electronic Structure/Function Correlations in Non-Heme Iron Enzymes Chem. Rev. 100, 235-350
10. Solomon, E. I., Decker, A., and Lehnert, N. (2003) Non-heme iron enzymes: Contrasts to heme catalysis Proc. Natl. Acad. Sci. U. S. A. 100, 3589-3594
11. Grzyska, P. K., Appelman, E. H., Hausinger, R. P., and Proshlyakov, D. A. (2010) Insight into the mechanism of an iron dioxygenase by resolution of steps following the FeIV=O species Proc. Natl. Acad. Sci. U. S. A. 107, 3982-3987
12. Pavel, E. G., Zhou, J., Busby, R. W., Gunsior, M., Townsend, C. A., and Solomon, E. I. (1998) Circular dichroism and magnetic circular dichroism spectroscopic studies of the non-heme ferrous active site in clavaminate synthase and its interaction with α-ketoglutarate cosubstrate J. Am. Chem. Soc. 120, 743-753
13. Light, K. M., Hangasky, J. A., Knapp, M. J., and Solomon, E. I. (2013) Spectroscopic studies of the mononuclear non-heme Fe(II) enzyme FIH: second-sphere contributions to reactivity J. Am. Chem. Soc. 135, 9665-9674
14. Price, J. C., Barr, E. W., Tirupati, B., Bollinger, J. M., and Krebs, C. (2003) The first direct characterization of a high-valent iron intermediate in the reaction of an α-ketoglutarate-dependent dioxygenase: a high-spin Fe(IV) complex in taurine/α-ketoglutarate dioxygenase (TauD) from Escherichia coli Biochemistry 42, 7497-7508
15. Krebs, C., Galonić Fujimori, D., Walsh, C. T., and Bollinger, J. M. (2007) Non-heme Fe(IV)-oxo intermediates Acc. Chem. Res. 40, 484-492
16. Price, J. C., Barr, E. W., Glass, T. E., Krebs, C., and Bollinger, J. M. (2003) Evidence for Hydrogen Abstraction from C1 of Taurine by the High-Spin Fe(IV) Intermediate Detected during Oxygen Activation by Taurine:α- Ketoglutarate Dioxygenase (TauD) J. Am. Chem. Soc. 125, 13008-13009
17. Riggs-Gelasco, P. J., Price, J. C., Guyer, R. B., Brehm, J. H., Barr, E. W., Bollinger, J. M., and Krebs, C. (2004) EXAFS Spectroscopic Evidence for an FeO Unit in the Fe(IV) Intermediate Observed during Oxygen Activation by Taurine:α-Ketoglutarate Dioxygenase J. Am. Chem. Soc. 126, 8108-8109
18. Baldwin, J. E., Adlington, R. M., Aplin, R. T., Crouch, N. P., Knight, G., and Schofield, C. J. (1987) Cephalosporin C biosynthesis; a branched pathway sensitive to a kinetic isotope effect J. Chem. Soc., Chem. Commun. 1651-1654
19. Townsend, C. A., Theis, A. B., Neese, A. S., Barrabee, E. B., and Poland, D. (1985) Stereochemical fate of chiral methyl of valine in the ring expansion of penicillin N to deacetoxycephalosporin C J. Am. Chem. Soc. 107, 4760-4767
20. Pang, C. P., White, R. L., Abraham, E. P., Crout, D. H., Lutstorf, M., Morgan, P. J., and Derome, A. E. (1984) Stereochemistry of the incorporation of valine methyl groups into methylene groups in cephalosporin C Biochem. J. 222, 777-788
21. Hewitson, K. S., Liénard, B. M. R., McDonough, M. A., Clifton, I. J., Butler, D., Soares, A. S., Oldham, N. J., McNeill, L. A., and Schofield, C. J. (2007) Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates J. Biol. Chem. 282, 3293-3301
22. Hamed, R. B., Gomez-Castellanos, J. R., Henry, L., Ducho, C., McDonough, M. A., and Schofield, C. J. (2013) The enzymes of β-lactam biosynthesis Nat. Prod. Rep. 30, 21-107
23. Baldwin, J. E., Adlington, R. M., Coates, J. B., Crabbe, M. J., Crouch, N. P., Keeping, J. W., Knight, G. C., Schofield, C. J., Ting, H. H., and Vallejo, C. A. (1987) Purification and initial characterization of an enzyme with deacetoxycephalosporin C synthetase and hydroxylase activities Biochem. J. 245, 831-841
24. Dotzlaf, J. E. and Yeh, W. K. (1987) Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium J. Bacteriol. 169, 1611-1618
25. Kovacevic, S., Weigel, B. J., Tobin, M. B., Ingolia, T. D., and Miller, J. R. (1989) Cloning, characterization, and expression in Escherichia coli of the Streptomyces clavuligerus gene encoding deacetoxycephalosporin C synthetase J. Bacteriol. 171, 754-760
26. Baker, B. J., Dotzlaf, J. E., and Yeh, W. K. (1991) Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication J. Biol. Chem. 266, 5087-5093
27. Rollins, M. J., Westlake, D. W. S., Wolfe, S., and Jensen, S. E. (1988) Purification and initial characterization of deacetoxycephalosporin C synthase from Streptomyces clavuligerus Can. J. Microbiol. 34, 1196-1202
28. Tahlan, K. and Jensen, S. E. (2013) Origins of the β-lactam rings in natural products J. Antibiot. 66, 401-410
29. Valegard, K., van Scheltinga, A. C. T., Lloyd, M. D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H.-J., Baldwin, J. E., Schofield, C. J., Hajdu, J., and Andersson, I. (1998) Structure of a cephalosporin synthase Nature 394, 805-809
30. Burzlaff, N. I., Rutledge, P. J., Clifton, I. J., Hensgens, C. M. H., Pickford, M., Adlington, R. M., Roach, P. L., and Baldwin, J. E. (1999) The reaction cycle of isopenicillin N synthase observed by X-ray diffraction Nature 401, 721-724
31. Freed, J. D., Hart, D. J., and Magomedov, N. A. (2001) Trapping of the putative cationic intermediate in the Morin rearrangement with carbon nucleophiles J. Org. Chem. 66, 839-852
32. Valegard, K., van Scheltinga, A. C. T., Dubus, A., Ranghino, G., Oster, L. M., Hajdu, J., and Andersson, I. (2004) The structural basis of cephalosporin formation in a mononuclear ferrous enzyme Nat. Struct. Mol. Biol. 11, 95-101
33. Baldwin, J. E., Adlington, R. M., Kang, T. W., Lee, E., and Schofield, C. J. (1988) The ring expansion of penama to cephams: a possible biomimetic process Tetrahedron 44, 5953-5957
34. Lloyd, M. D., Lee, H.-J., Harlos, K., Zhang, Z.-H., Baldwin, J. E., Schofield, C. J., Charnock, J. M., Garner, C. D., Hara, T., Terwisscha van Scheltinga, A. C., Valegård, K., Viklund, J. A. C., Hajdu, J., Andersson, I., Danielsson, Å., and Bhikhabhai, R. (1999) Studies on the active site of deacetoxycephalosporin C synthase J. Mol. Biol. 287, 943-960
35. Mecinović, J., Chowdhury, R., Flashman, E., and Schofield, C. J. (2009) Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2 Anal. Biochem. 393, 215-221
36. Leung, I. K. H., Flashman, E., Yeoh, K. K., Schofield, C. J., and Claridge, T. D. W. (2010) Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions J. Med. Chem. 53, 867-875
37. Bertini, I., Fragai, M., Luchinat, C., and Talluri, E. (2008) Water-Based Ligand Screening for Paramagnetic Metalloproteins Angew. Chem., Int. Ed. 47, 4533-4537
38. Morton, C. J., Pugh, D. J. R., Brown, E. L. J., Kahmann, J. D., Renzoni, D. A. C., and Campbell, I. D. (1996) Solution structure and peptide binding of the SH3 domain from human Fyn Structure 4, 705-714
39. Leung, I. K. H., Demetriades, M., Hardy, A. P., Lejeune, C., Smart, T. J., Szöllössi, A., Kawamura, A., Schofield, C. J., and Claridge, T. D. W. (2013) Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors J. Med. Chem. 56, 547-555
40. McNeill, L. A., Flashman, E., Buck, M. R. G., Hewitson, K. S., Clifton, I. J., Jeschke, G., Claridge, T. D. W., Ehrismann, D., Oldham, N. J., and Schofield, C. J. (2005) Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate Mol. Biosyst. 1, 321-324
41. McDonough, M. A., Li, V., Flashman, E., Chowdhury, R., Mohr, C., Liénard, B. M. R., Zondlo, J., Oldham, N. J., Clifton, I. J., Lewis, J., McNeill, L. A., Kurzeja, R. J. M., Hewitson, K. S., Yang, E., Jordan, S., Syed, R. S., and Schofield, C. J. (2006) Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2) Proc. Natl. Acad. Sci. U. S. A. 103, 9814-9819
42. Warshakoon, N. C., Wu, S., Boyer, A., Kawamoto, R., Sheville, J., Renock, S., Xu, K., Pokross, M., Evdokimov, A. G., Walter, R., and Mekel, M. (2006) A novel series of imidazo[1,2-a]pyridine derivatives as HIF-1α prolyl hydroxylase inhibitors Bioorg. Med. Chem. Lett. 16, 5598-5601
43. Aik, W., Demetriades, M., Hamdan, M. K. K., Bagg, E. A. L., Yeoh, K. K., Lejeune, C., Zhang, Z., McDonough, M. A., and Schofield, C. J. (2013) Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO) J. Med. Chem. 56, 3680-3688
44. Ryle, M. J., Padmakumar, R., and Hausinger, R. P. (1999) Stopped-flow kinetic analysis of Escherichia coli taurine/α-ketoglutarate dioxygenase: interactions with α-ketoglutarate, taurine, and oxygen Biochemistry 38, 15278-15286
45. 2- and α-Ketoglutarate-Dependent Tyrosyl Radical Formation in TauD, an α-Keto Acid-Dependent Non-Heme Iron Dioxygenase Biochemistry 42, 1854-1862
46. Hoffart, L. M., Barr, E. W., Guyer, R. B., Bollinger, J. M., and Krebs, C. (2006) Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a prolyl-4-hydroxylase Proc. Natl. Acad. Sci. U. S. A. 103, 14738-14743
47. Sánchez-Fernández, E. M., Tarhonskaya, H., Al-Qahtani, K., Hopkinson, R. J., McCullagh, J. S. O., Schofield, C. J., and Flashman, E. (2013) Investigations on the oxygen dependence of a 2-oxoglutarate histone demethylase Biochem. J. 449, 491-496
48. Grzyska, P. K., Ryle, M. J., Monterosso, G. R., Liu, J., Ballou, D. P., and Hausinger, R. P. (2005) Steady-State and Transient Kinetic Analyses of Taurine/α-Ketoglutarate Dioxygenase: Effects of Oxygen Concentration, Alternative Sulfonates, and Active-Site Variants on the FeIV-oxo Intermediate Biochemistry 44, 3845-3855
49. Galonic, D. P., Barr, E. W., Walsh, C. T., Bollinger, J. M., and Krebs, C. (2007) Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3 Nat. Chem. Biol. 3, 113-116
50. Matthews, M. L., Krest, C. M., Barr, E. W., Vaillancourt, F. d. r. H., Walsh, C. T., Green, M. T., Krebs, C., and Bollinger, J. M. (2009) Substrate-triggered formation and remarkable stability of the C-H bond-cleaving chloroferryl Intermediate in the aliphatic halogenase, SyrB2 Biochemistry 48, 4331-4343
51. Flashman, E., Hoffart, L. M., Hamed, R. B., Bollinger, J. M., Jr, Krebs, C., and Schofield, C. J. (2010) Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen FEBS J. 277, 4089-4099
52. Price, J. C., Barr, E. W., Hoffart, L. M., Krebs, C., and Bollinger, J. M. (2005) Kinetic Dissection of the Catalytic Mechanism of Taurine:α- Ketoglutarate Dioxygenase (TauD) from Escherichia coli Biochemistry 44, 8138-8147
53. Hewitson, K. S., Granatino, N., Welford, R. W. D., McDonough, M. A., and Schofield, C. J. (2005) Oxidation by 2-oxoglutarate oxygenases: non-haem iron systems in catalysis and signalling Philos. Trans. Math. Phys. Eng. Sci. 363, 807-828
54. Lee, H.-J., Lloyd, M. D., Harlos, K., Clifton, I. J., Baldwin, J. E., and Schofield, C. J. (2001) Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS) J. Mol. Biol. 308, 937-948
55. Lee, H.-J., Schofield, C. J., and Lloyd, M. D. (2002) Active site mutations of recombinant Deacetoxycephalosporin C Synthase Biochem. Biophys. Res. Commun. 292, 66-70
56. Ji, J., Tian, X., Fan, K., and Yang, K. (2012) New strategy of site-directed mutagenesis identifies new sites to improve Streptomyces clavuligerus deacetoxycephalosporin C synthase activity toward penicillin G Appl. Microbiol. Biotechnol. 93, 2395-2401
57. Wei, C.-L., Yang, Y.-B., Wang, W.-C., Liu, W.-C., Hsu, J.-S., and Tsai, Y.-C. (2003) Engineering streptomyces clavuligerus deacetoxycephalosporin C synthase for optimal ring expansion activity toward penicillin G Appl. Environ. Microbiol. 69, 2306-2312
58. Baldwin, J. E., Adlington, R. M., Crouch, N. P., Schofield, C. J., Turner, N. J., and Aplin, R. T. (1991) Cephalosporin biosynthesis: A branched pathway sensitive to an isotope effect Tetrahedron 47, 9881-9900
59. Öster, L. M., van Scheltinga, A. C. T., Valegård, K., Hose, A. M., Dubus, A., Hajdu, J., and Andersson, I. (2004) Conformational flexibility of the C terminus with implications for substrate binding and catalysis revealed in a new crystal form of deacetoxycephalosporin C synthase J. Mol. Biol. 343, 157-171
60. Chin, H. S. and Sim, T. S. (2002) C-terminus modification of Streptomyces clavuligerus deacetoxycephalosporin C synthase improves catalysis with an expanded substrate specificity Biochem. Biophys. Res. Commun. 295, 55-61
61. Lloyd, M. D., Lipscomb, S. J., Hewitson, K. S., Hensgens, C. M. H., Baldwin, J. E., and Schofield, C. J. (2004) Controlling the substrate selectivity of deacetoxycephalosporin/deacetylcephalosporin C synthase J. Biol. Chem. 279, 15420-15426
62. Chowdhury, R., McDonough, M. A., Mecinović, J., Loenarz, C., Flashman, E., Hewitson, K. S., Domene, C., and Schofield, C. J. (2009) Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases Structure 17, 981-989
63. Flashman, E., Bagg, E. A. L., Chowdhury, R., Mecinović, J., Loenarz, C., McDonough, M. A., Hewitson, K. S., and Schofield, C. J. (2008) Kinetic rationale for selectivity toward N- and C-terminal oxygen-dependent degradation domain substrates mediated by a loop region of hypoxia-Inducible factor prolyl hydroxylases J. Biol. Chem. 283, 3808-3815
64. Chin, H. S., Sim, J., and Sim, T. S. (2001) Mutation of N304 to leucine in Streptomyces clavuligerus deacetoxycephalosporin C synthase creates an enzyme with increased penicillin analogue conversion Biochem. Biophys. Res. Commun. 287, 507-513
65. Goo, K. S., Chua, C. S., and Sim, T.-S. (2008) A complete library of amino acid alterations at R306 in Streptomyces clavuligerus deacetoxycephalosporin C synthase demonstrates its structural role in the ring-expansion activity Proteins: Struct., Funct., Bioinf. 70, 739-747
66. Goo, K. S., Chua, C. S., and Sim, T.-S. (2008) Relevant double mutations in bioengineered Streptomyces clavuligerus deacetoxycephalosporin C synthase result in higher binding specificities which improve penicillin bioconversion Appl. Environ. Microbiol. 74, 1167-1175
67. Goo, K.-S., Chua, C.-S., and Sim, T.-S. (2009) Directed evolution and rational approaches to improving Streptomyces clavuligerus deacetoxycephalosporin C synthase for cephalosporin production J. Ind. Microbiol. Biotechnol. 36, 619-633
68. Mantri, M., Zhang, Z., McDonough, M. A., and Schofield, C. J. (2012) Autocatalysed oxidative modifications to 2-oxoglutarate dependent oxygenases FEBS J. 279, 1563-1575