1e9c: Difference between revisions
New page: left|200px<br /> <applet load="1e9c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1e9c, resolution 1.6Å" /> '''MUTANT HUMAN THYMIDY... |
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==About this Structure== | ==About this Structure== | ||
1E9C is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with MG, TMP and ADP as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[http://en.wikipedia.org/wiki/ ]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1E9C OCA]]. | 1E9C is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with MG, TMP and ADP as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9]]. Structure known Active Site: TMP. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1E9C OCA]]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: dTMP kinase]] | |||
[[Category: Brundiers, R.]] | [[Category: Brundiers, R.]] | ||
[[Category: Goody, R.S.]] | [[Category: Goody, R.S.]] | ||
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[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
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Revision as of 12:45, 30 October 2007
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MUTANT HUMAN THYMIDYLATE KINASE COMPLEXED WITH TMP AND APPNP
OverviewOverview
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 StructureAbout this Structure
1E9C is a [Single protein] structure of sequence from [Homo sapiens] with MG, TMP and ADP as [ligands]. Active as [dTMP kinase], with EC number [2.7.4.9]. Structure known Active Site: TMP. Full crystallographic information is available from [OCA].
ReferenceReference
Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP., Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I, J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809
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