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| | {{STRUCTURE_5tmp| PDB=5tmp | SCENE= }} | | {{STRUCTURE_5tmp| PDB=5tmp | SCENE= }} |
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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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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_9826650}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9826650 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9826650}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Schlichting, I.]] | | [[Category: Schlichting, I.]] |
| | [[Category: Atp:dtmp phosphotransferase]] | | [[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 Thu Jul 3 14:12:01 2008'' |
Revision as of 11:12, 3 July 2008
Template:STRUCTURE 5tmp
COMPLEX OF E. COLI THYMIDYLATE KINASE WITH THE BISUBSTRATE INHIBITOR AZTP5A
Template:ABSTRACT PUBMED 9826650
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 Thu Jul 3 14:12:01 2008
