1e2q
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1e2q.gif|left|200px]] | [[Image:1e2q.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1e2q", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1e2q| PDB=1e2q | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH TP5A AND A MAGNESIUM-ION''' | '''HUMAN THYMIDYLATE KINASE COMPLEXED WITH TP5A AND A MAGNESIUM-ION''' | ||
| Line 25: | Line 22: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: | + | [[Category: DTMP kinase]] |
[[Category: Brundiers, R.]] | [[Category: Brundiers, R.]] | ||
[[Category: Goody, R S.]] | [[Category: Goody, R S.]] | ||
| Line 34: | Line 31: | ||
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
[[Category: Veit, T.]] | [[Category: Veit, T.]] | ||
| - | [[Category: | + | [[Category: P-loop]] |
| - | [[Category: | + | [[Category: Thymidylate kinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:35:08 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:35, 2 May 2008
HUMAN THYMIDYLATE KINASE COMPLEXED WITH TP5A AND A MAGNESIUM-ION
Overview
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 Structure
1E2Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:10873853 Page seeded by OCA on Fri May 2 14:35:08 2008
