1e9a: Difference between revisions
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==Overview== | ==Overview== | ||
The 60-fold reduced phosphorylation rate of azidothymidine (AZT) | The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: dTMP kinase]] | [[Category: dTMP kinase]] | ||
[[Category: Brundiers, R.]] | [[Category: Brundiers, R.]] | ||
[[Category: Goody, R | [[Category: Goody, R S.]] | ||
[[Category: Konrad, M.]] | [[Category: Konrad, M.]] | ||
[[Category: Lavie, A.]] | [[Category: Lavie, A.]] | ||
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[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:25:21 2008'' | ||