1E9F: Mutant Human Thymidylate Kinase Complexed With Tmp And Adp

Citation:
Abstract
The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.
PDB ID: 1E9FDownload
MMDB ID: 17794
PDB Deposition Date: 2000/10/11
Updated in MMDB: 2001/11
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Similar Structures:
Biological Unit for 1E9F: dimeric; determined by author and by software (PQS)
Molecular Components in 1E9F
Label Count Molecule
Proteins (2 molecules)
2
Thymidylate Kinase(Gene symbol: DTYMK)
Molecule annotation
Chemicals (7 molecules)
1
2
2
2
3
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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