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PDBsum entry 1kim
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Exploring the active site of herpes simplex virus type-1 thymidine kinase by x-Ray crystallography of complexes with aciclovir and other ligands.
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Authors
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J.N.Champness,
M.S.Bennett,
F.Wien,
R.Visse,
W.C.Summers,
P.Herdewijn,
E.De clerq,
T.Ostrowski,
R.L.Jarvest,
M.R.Sanderson.
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Ref.
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Proteins, 1998,
32,
350-361.
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PubMed id
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Abstract
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Antiherpes therapies are principally targeted at viral thymidine kinases and
utilize nucleoside analogs, the triphosphates of which are inhibitors of viral
DNA polymerase or result in toxic effects when incorporated into DNA. The most
frequently used drug, aciclovir (Zovirax), is a relatively poor substrate for
thymidine kinase and high-resolution structural information on drugs and other
molecules binding to the target is therefore important for the design of novel
and more potent chemotherapy, both in antiherpes treatment and in gene therapy
systems where thymidine kinase is expressed. Here, we report for the first time
the binary complexes of HSV-1 thymidine kinase (TK) with the drug molecules
aciclovir and penciclovir, determined by X-ray crystallography at 2.37 A
resolution. Moreover, from new data at 2.14 A resolution, the refined structure
of the complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all
data) now reveals much detail concerning substrate and solvent interactions with
the enzyme. Structures of the complexes of TK with four halogen-containing
substrate analogs have also been solved, to resolutions better than 2.4 A. The
various TK inhibitors broadly fall into three groups which together probe the
space of the enzyme active site in a manner that no one molecule does alone, so
giving a composite picture of active site interactions that can be exploited in
the design of novel compounds.
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Secondary reference #1
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Title
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3'-Amino thymidine affinity matrix for the purification of herpes simplex virus thymidine kinase.
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Authors
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P.P.Tung,
J.Respass,
W.C.Summers.
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Ref.
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Yale J Biol Med, 1996,
69,
495-503.
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PubMed id
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Secondary reference #2
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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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Secondary reference #3
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Title
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The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1.
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Authors
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D.J.Mcgeoch,
M.A.Dalrymple,
A.J.Davison,
A.Dolan,
M.C.Frame,
D.Mcnab,
L.J.Perry,
J.E.Scott,
P.Taylor.
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Ref.
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J Gen Virol, 1988,
69,
1531-1574.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Purification and crystallization of thymidine kinase from herpes simplex virus type 1.
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Authors
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M.R.Sanderson,
P.S.Freemont,
H.M.Murthy,
J.F.Krane,
W.C.Summers,
T.A.Steitz.
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Ref.
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J Mol Biol, 1988,
202,
917-919.
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PubMed id
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Secondary reference #5
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Title
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Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1.
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Authors
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M.J.Wagner,
J.A.Sharp,
W.C.Summers.
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Ref.
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Proc Natl Acad Sci U S A, 1981,
78,
1441-1445.
[DOI no: ]
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PubMed id
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