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Title
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Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir.
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Authors
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D.G.Brown,
R.Visse,
G.Sandhu,
A.Davies,
P.J.Rizkallah,
C.Melitz,
W.C.Summers,
M.R.Sanderson.
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Ref.
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Nat Struct Biol, 1995,
2,
876-881.
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PubMed id
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Abstract
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The crystal structures of thymidine kinase from herpes simplex virus type-1
complexed with its natural substrate deoxythymidine (dT) and complexed with the
guanosine analogue Ganciclovir have been solved. Both structures are in the
C222(1) crystal form with two molecules per asymmetric unit related by a
non-crystallographic two-fold axis. The present models have been refined to 2.8
A and 2.2 A, with crystallographic R factors of 24.1% and 23.3% for the dT and
Ganciclovir complexes respectively, without the inclusion of any solvent
molecules. The core of the molecule exhibits high structural homology with
adenylate kinase and other nucleotide binding proteins. These structural
similarities provide an insight into the mechanism of nucleoside phosphorylation
by thymidine kinase.
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