1e9a: Difference between revisions
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[[Image:1e9a.jpg|left|200px]]<br /><applet load="1e9a" size=" | [[Image:1e9a.jpg|left|200px]]<br /><applet load="1e9a" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1e9a, resolution 1.6Å" /> | caption="1e9a, resolution 1.6Å" /> | ||
'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR AZTP5A'''<br /> | '''HUMAN THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR AZTP5A'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1E9A 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 and Z5A 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] Known structural/functional Site: <scene name='pdbsite=Z5A:The Bisubstrate Inhibitor Binding Site Residue Z5a A 301'>Z5A</scene>. Full crystallographic information is available from [http:// | 1E9A 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 <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=Z5A:'>Z5A</scene> 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] Known structural/functional Site: <scene name='pdbsite=Z5A:The+Bisubstrate+Inhibitor+Binding+Site+Residue+Z5a+A+301'>Z5A</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E9A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
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Revision as of 10:38, 3 February 2008
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HUMAN THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR AZTP5A
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
1E9A is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as dTMP kinase, with EC number 2.7.4.9 Known structural/functional Site: . 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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