Abstract
The dihydropteridine reductase (DHPR) gene from rat liver has recently been cloned1 and the protein that was expressed from the cDNA was crystallised as the binary DHPR-NADH complex.2 The X-ray structure of the enzyme was determined and although the exact location of NADH in the enzyme was determined in the binary complex, the precise position of the pteridine cofactor was not obtained and had to be deduced from known kinetic data of various pteridine cofactor analogues.2 In order to obtain the precise position of the pteridine cofactor it is necessary to crystallise the ternary complex of DHPR, NADH and an inhibitor whose structure is so close to that of a viable cofactor (eg 1) that it would bind at the active site in the same manner as the pterin.
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References
M.Shahbaz, J.A.Hoch, K.A.Trach, J.A.Hural, S.Webber and J.M.Whiteley, (1987) J.Biol.Chem. ,262, 16412–16416
K.I.Varughese, M.M.Skinner, J.M.Whiteley, D.A.Matthews and N.H.Xuong, (1992) Proc.Natl.Acad.Sci.USA ,89, 6080–6084
J.E.Craine, E.S.Hall and S.Kaufman (1972) J.Biol.Chem. 247, 6082–6091
K.E.Lind (1972) Eur.J. Biochem. 25, 560–562
M.M.Chauvin, K.K.Korri, A.Tripak, R.C.Simpson and K.G.Scrimgeour (1978) Can.J.Biochem. 57, 178–187
S.Cheema, S.J.Soldin, A.Knapp, T.Hofmann and K.G.Scrimgeour (1973) Can.J. Biochem. 51, 1229–1239
W. L. F. Armarego, (1989) Pteridines ,1, 179
P. Waring and W. L. F. Armarego, (1987) Eur. J. Medicinal Chem. ,22, 83
H. Neunhoffer and P. F. Wiley, Heterocyclic Compounds: Chemistry of 1,2,3-Triazines, 1,2,4-Triazines, Tetrazines and Pentazines, J.Wiley and Sons, 33, pp.797–842 (1978)
T. Sugimoto and S. Matsuura, (1975) Bull. Chem. Soc. Japan ,48, 1679
D. Randies, H. Taguchi and W. L. F. Armarego, (1993) Heterocycles ,(in press)
J. P. Horowitz and C. C. Rila, (1958) J. Am. Chem. Soc. ,80, 431;
S. J. Angyal and K. Warburton, (1951) J. Chem. Soc. ,2492
C.M. Hardy, B. Paal, P. Smooker, R. G. H. Cotton, P. Carr, D. L. Ollis, and W. L. F. Armarego, (1993 unpublished results)
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Randles, D., Taguchi, H., Armarego, W.L.F. (1993). New Inhibitors of Dihydropteridine Reductase (Human Brain). In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_25
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_25
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