Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation

Nature

Volumn 387, Issue 6635, 1997, Pages 827-830

  Roach, Peter L ^a   Clifton, Ian J ^a   Hensgens, Charles M H ^a   Shibata, Norio ^a   Schofield, Christopher J ^a   Hajdu, Janos ^b   Baldwin, Jack E ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CEPHALOSPORIN DERIVATIVE; ISOPENICILLIN N SYNTHETASE; PENICILLIN G;

ANTIBIOTIC BIOSYNTHESIS; ARTICLE; DRUG STRUCTURE; ENZYME ACTIVITY; PRIORITY JOURNAL; REACTION ANALYSIS; STRUCTURE ANALYSIS;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; FERROUS COMPOUNDS; HYDROGEN BONDING; MODELS, MOLECULAR; OLIGOPEPTIDES; OXIDOREDUCTASES; OXYGEN; PENICILLINS; PROTEIN CONFORMATION;

EID: 0030947388     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/42990     Document Type: Article

References (30)

1. Baldwin, J. E. & Abraham, E. Biosynthesis of penicillins and cephalosporins. Nat. Prod. Rep. 5, 129-145 (1988).
2. Pang, C. P. et al. Purification of isopenicillin N synthetase. Biochem. J. 222, 789-795 (1984).
3. Baldwin, J. E. & Schofield, C. J. in The Chemistry of β-lactams (ed. Page, M. I.) 1-78 (Blackie, London, 1992).
4. Que, L. & Ho, R. Y. N. Dioxygen activation by enzymes with mononuclear non-haem iron active sites. Chem. Rev. 96, 2607-2624 (1996).
5. Orville, A. M. et al. Thiolate ligation of the active site iron(II) of isopenicillin N synthase derives from substrate rather than endogenous cysteine: spectroscopic studies of site-specific Cys → Ser mutated enzymes. Biochemistry 31, 4602-4612 (1992).
6. Randall, C. R. et al. X-ray absorption studies of the ferrous active site of isopenicillin N synthase and related model complexes. Biochemistry 32, 6664-6673 (1993).
7. Roach, P. L. et al. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature 375, 700-704 (1995).
8. Roach, P. L. et al. Anaerobic crystallisation of an isopenicillin N synthase.Fe(II).substrate complex demonstrated by X-ray studies. Eur. J. Biochem. 242, 736-740 (1996).
9. Borovok, I., Landman, O., Kreisberg-Zakarin, R., Aharonowitz, Y. & Cohen, G. Ferrous active site of isopenicillin N synthase: genetic and sequence analysis of endogenous ligands. Biochemistry 35, 1981-1987 (1996).
10. 2+ oxidase with metal coordination sites for small molecules and substrate. J. Biol. Chem. 264, 21677-21681 (1989).
11. Baldwin, J. E. et al. Penicillin biosynthesis: active site mapping with aminoadipoylcysteinylvaline variants. J. Chem. Soc. Chem. Commun. 1225-1227 (1984).
12. Rowe, C. J. thesis, Oxford Univ. (1995).
13. Hadfield, A. & Hajdu, J. A fast and portable microspectrophotometer for protein crystallography. J. Appl. Crystallogr. 26, 839-842 (1993).
14. Cooper, R. D. G. The enzymes involved in biosynthesis of penicillin and cephalosporin: Their structure and function. Bioorg. Med. Chem. 1, 1-17 (1993).
15. Baldwin, J. E. et al. Evidence for an insertion-homolysis mechanism for carbon-sulfur bond formation in penicillin biosynthesis; 2. Incubation and interpretation. Tetrahedron 52, 2537-2556 (1996).
16. Groves, J. T. & Han, Y. Z. in Cytochrome P-450: Structure, Chemistry and Biochemistry 2nd edn (ed. Ortiz de Montellano, P. R.) 3-49 (Plenum, New York, 1995).
17. Baldwin, J. E., Morris, G. M. & Richards, W. G. Electron transport in cytochromes P-450 by covalent switching. Proc. R. Soc. Lond. B 245, 43-52 (1991).
18. Prescott, A. G. A dilemma of dioxygenases (or where biochemistry and molecular biology fail to meet). J. Exp. Bol. 44, 849-861 (1993).
19. Hanauske-Abel, H. M. & Guzzler, V. A stereochemical concept for the catalytic mechanism of prolylhydroxylase. J. Theor. Biol. 94, 421-455 (1982).
20. Shu, L. et al. X-ray absorption spectroscopic studies of the Fe(II) active site of catechol 2,3-dioxygenase. Implications for the extradiol cleavage mechanism. Biochemistry 34, 6649-6659 (1995).
21. Han, S., Eltis, L. D., Timmis, K. N., Muchmore, S. W. & Bolin, J. T. Crystal structure of the biphenyl-cleaving extradiol dioxygenase from a PCB-degrading pseudomonad. Science 270, 976-980 (1995).
22. Senda, T. et al. Three-dimensional structures of free form and two substrate complexes of an extradiol ring-cleavage type dioxygenase, the BphC enzyme from Pseudommas sp. strain KKS102. J. Mol. Biol. 255, 735-752 (1996).
23. Otwinowski, Z. in Data Collection and Processing (eds Sawyer, L., Isaacs, N. W. & Bailey, S.) 55-62 (Daresbury Laboratory, Warrington, UK, 1993).
24. Navaza, J. AMoRe: an automated package for molecular replacement. Acta Crystallogr. A 50, 157-163 (1994).
25. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjelgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110-119 (1991).
26. Brünger, A. T., Kuriyan, J. & Karplus, M. Crystallography R factor refinement by molecular dynamics. Science 235, 458-460 (1987).
27. Konnert, J. H. & Hendrickson, W. A. A restrained-parameter thermal-factor refinement procedure. Acta Crystallogr. A 36, 344-350 (1980).
28. Sheldrick, G. M. SHELXL93, Program for Crystal Structure Refinement (Univ. Gottingen, Germany, 1993).
29. Leslie, A. G. W. Mosflm (MRC Laboratory of Molecular Biology, Cambridge, 1996).
30. CCP4 The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).