5tmp
From Proteopedia
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'''COMPLEX OF E. COLI THYMIDYLATE KINASE WITH THE BISUBSTRATE INHIBITOR AZTP5A''' | '''COMPLEX OF E. COLI THYMIDYLATE KINASE WITH THE BISUBSTRATE INHIBITOR AZTP5A''' | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: | + | [[Category: DTMP kinase]] |
[[Category: Lavie, A.]] | [[Category: Lavie, A.]] | ||
[[Category: Ostermann, N.]] | [[Category: Ostermann, N.]] | ||
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
| - | [[Category: | + | [[Category: Atp:dtmp phosphotransferase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:38:08 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:38, 4 May 2008
COMPLEX OF E. COLI THYMIDYLATE KINASE WITH THE BISUBSTRATE INHIBITOR AZTP5A
Overview
The crystal structures of Escherichia coli thymidylate kinase (TmpK) in complex with P1-(5'-adenosyl)-P5-(5'-thymidyl)pentaphosphate and P1-(5'-adenosyl)P5-[5'-(3'-azido-3'-deoxythymidine)] pentaphosphate have been solved to 2.0-A and 2.2-A resolution, respectively. The overall structure of the bacterial TmpK is very similar to that of yeast TmpK. In contrast to the human and yeast TmpKs, which phosphorylate 3'-azido-3'-deoxythymidine 5'-monophosphate (AZT-MP) at a 200-fold reduced turnover number (kcat) in comparison to the physiological substrate dTMP, reduction of kcat is only 2-fold for the bacterial enzyme. The different kinetic properties toward AZT-MP between the eukaryotic TmpKs and E. coli TmpK can be rationalized by the different ways in which these enzymes stabilize the presumed transition state and the different manner in which a carboxylic acid side chain in the P loop interacts with the deoxyribose of the monophosphate. Yeast TmpK interacts with the 3'-hydroxyl of dTMP through Asp-14 of the P loop in a bidentate manner: binding of AZT-MP results in a shift of the P loop to accommodate the larger substituent. In E. coli TmpK, the corresponding residue is Glu-12, and it interacts in a side-on fashion with the 3'-hydroxyl of dTMP. This different mode of interaction between the P loop carboxylic acid with the 3' substituent of the monophosphate deoxyribose allows the accommodation of an azido group in the case of the E. coli enzyme without significant P loop movement. In addition, although the yeast enzyme uses Arg-15 (a glycine in E. coli) to stabilize the transition state, E. coli seems to use Arg-153 from a region termed Lid instead. Thus, the binding of AZT-MP to the yeast TmpK results in the shift of a catalytic residue, which is not the case for the bacterial kinase.
About this Structure
5TMP is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structural basis for efficient phosphorylation of 3'-azidothymidine monophosphate by Escherichia coli thymidylate kinase., Lavie A, Ostermann N, Brundiers R, Goody RS, Reinstein J, Konrad M, Schlichting I, Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14045-50. PMID:9826650 Page seeded by OCA on Sun May 4 22:38:08 2008
