1e2g: Difference between revisions
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[[Image:1e2g.gif|left|200px]] | [[Image:1e2g.gif|left|200px]] | ||
'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH ADP, TDP AND A MAGNESIUM-ION''' | {{Structure | ||
|PDB= 1e2g |SIZE=350|CAPTION= <scene name='initialview01'>1e2g</scene>, resolution 1.7Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5'-PHOSPHATE'>TMP</scene>, <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=TYD:THYMIDINE-5'- DIPHOSPHATE'>TYD</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] | |||
|GENE= | |||
}} | |||
'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH ADP, TDP AND A MAGNESIUM-ION''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1E2G is a [ | 1E2G is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E2G OCA]. | ||
==Reference== | ==Reference== | ||
Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate., Ostermann N, Schlichting I, Brundiers R, Konrad M, Reinstein J, Veit T, Goody RS, Lavie A, Structure. 2000 Jun 15;8(6):629-42. PMID:[http:// | Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate., Ostermann N, Schlichting I, Brundiers R, Konrad M, Reinstein J, Veit T, Goody RS, Lavie A, Structure. 2000 Jun 15;8(6):629-42. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10873853 10873853] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:48:31 2008'' | ||
Revision as of 11:48, 20 March 2008
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| , resolution 1.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | dTMP kinase, with EC number 2.7.4.9 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN THYMIDYLATE KINASE COMPLEXED WITH ADP, TDP AND A MAGNESIUM-ION
OverviewOverview
BACKGROUND: Thymidylate kinase (TMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryltransfer between ATP and TMP to yield ADP and TDP. In addition to its vital role in supplying precursors for DNA synthesis, human TMPK has an important medical role participating in the activation of a number of anti-HIV prodrugs. RESULTS: Crystal structures of human TMPK in complex with TMP and ADP, TMP and the ATP analog AppNHp, TMP with ADP and the phosphoryl analog AlF(3), TDP and ADP, and the bisubstrate analog TP(5)A were determined. The conformations of the P-loop, the LID region, and the adenine-binding loop vary according to the nature of the complex. Substitution of ADP by AppNHp results in partial closure of the P-loop and the rotation of the TMP phosphate group to a catalytically unfavorable position, which rotates back in the AlF(3) complex to a position suitable for in-line attack. In the fully closed state observed in the TP(5)A and the TDP-ADP complexes, Asp15 interacts strongly with the 3'-hydroxyl group of TMP. CONCLUSIONS: The observed changes of nucleotide state and conformation and the corresponding protein structural changes are correlated with intermediates occurring along the reaction coordinate and show the sequence of events occurring during phosphate transfer. The low catalytic activity of human TMPK appears to be determined by structural changes required to achieve catalytic competence and it is suggested that a mechanism might exist to accelerate the activity.
About this StructureAbout this Structure
1E2G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate., Ostermann N, Schlichting I, Brundiers R, Konrad M, Reinstein J, Veit T, Goody RS, Lavie A, Structure. 2000 Jun 15;8(6):629-42. PMID:10873853
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