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New Inhibitors of Dihydropteridine Reductase (Human Brain)

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Chemistry and Biology of Pteridines and Folates

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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© 1993 Springer Science+Business Media New York

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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

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6287-6

  • Online ISBN: 978-1-4615-2960-6

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