5tmp
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=Z5A:P1-(5'-ADENOSYL)P5-(5'-(3'AZIDO-3'-DEOXYTHYMIDYL))PENTAPHOSPHATE'>Z5A</scene> | |LIGAND= <scene name='pdbligand=Z5A:P1-(5'-ADENOSYL)P5-(5'-(3'AZIDO-3'-DEOXYTHYMIDYL))PENTAPHOSPHATE'>Z5A</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=5tmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tmp OCA], [http://www.ebi.ac.uk/pdbsum/5tmp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=5tmp RCSB]</span> | ||
}} | }} | ||
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[[Category: Ostermann, N.]] | [[Category: Ostermann, N.]] | ||
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
| - | [[Category: Z5A]] | ||
[[Category: atp:dtmp phosphotransferase]] | [[Category: atp:dtmp phosphotransferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:42:25 2008'' |
Revision as of 02:42, 31 March 2008
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| , resolution 1.98Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | dTMP kinase, with EC number 2.7.4.9 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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