1e9c: Difference between revisions
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|PDB= 1e9c |SIZE=350|CAPTION= <scene name='initialview01'>1e9c</scene>, resolution 1.6Å | |PDB= 1e9c |SIZE=350|CAPTION= <scene name='initialview01'>1e9c</scene>, resolution 1.6Å | ||
|SITE= <scene name='pdbsite=TMP:Anp+Binding+Site'>TMP</scene> | |SITE= <scene name='pdbsite=TMP:Anp+Binding+Site'>TMP</scene> | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-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'-PHOSPHATE'>TMP</scene> | ||
|ACTIVITY= [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] | |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> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|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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[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
[[Category: Veit, T.]] | [[Category: Veit, T.]] | ||
[[Category: p-loop]] | [[Category: p-loop]] | ||
[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:57:55 2008'' | ||
Revision as of 19:57, 30 March 2008
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| , resolution 1.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | dTMP kinase, with EC number 2.7.4.9 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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