1e9c

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[[Image:1e9c.jpg|left|200px]]
[[Image:1e9c.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1e9c |SIZE=350|CAPTION= <scene name='initialview01'>1e9c</scene>, resolution 1.6&Aring;
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The line below this paragraph, containing "STRUCTURE_1e9c", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=TMP:Anp+Binding+Site'>TMP</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5&#39;-PHOSPHATE'>TMP</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1e9c| PDB=1e9c | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9c OCA], [http://www.ebi.ac.uk/pdbsum/1e9c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e9c RCSB]</span>
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}}
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'''MUTANT HUMAN THYMIDYLATE KINASE COMPLEXED WITH TMP AND APPNP'''
'''MUTANT HUMAN THYMIDYLATE KINASE COMPLEXED WITH TMP AND APPNP'''
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: dTMP kinase]]
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[[Category: DTMP kinase]]
[[Category: Brundiers, R.]]
[[Category: Brundiers, R.]]
[[Category: Goody, R S.]]
[[Category: Goody, R S.]]
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[[Category: Schlichting, I.]]
[[Category: Schlichting, I.]]
[[Category: Veit, T.]]
[[Category: Veit, T.]]
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[[Category: p-loop]]
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[[Category: P-loop]]
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[[Category: thymidylate kinase]]
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[[Category: Thymidylate kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:49:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:57:55 2008''
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Revision as of 11:49, 2 May 2008

Image:1e9c.jpg

Template:STRUCTURE 1e9c

MUTANT HUMAN THYMIDYLATE KINASE COMPLEXED WITH TMP AND APPNP


Overview

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

1E9C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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 Page seeded by OCA on Fri May 2 14:49:40 2008

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OCA

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