DB code: S00302

RLCP classification 3.103.70000.350 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.7.1.21
CSA 1kim
M-CSA 1kim
MACiE

CATH domain Related DB codes (homologues)
3.40.50.300 : Rossmann fold S00527 S00547 S00548 S00550 S00554 S00555 S00671 S00672 S00676 S00680 S00682 S00913 S00914 S00301 S00303 S00304 S00307 S00308 S00305 S00306 S00309 S00310 S00311 M00114 M00199 D00129 D00130 D00540 M00186

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P03176 Thymidine kinase
EC 2.7.1.21
NP_044624.1 (Protein)
NC_001806.1 (DNA/RNA sequence)
PF00693 (Herpes_TK)
[Graphical View]
P06479 Thymidine kinase
EC 2.7.1.21
PF00693 (Herpes_TK)
[Graphical View]
P24425 Thymidine kinase
EC 2.7.1.21
PF00693 (Herpes_TK)
[Graphical View]
P0C0E6 Thymidine kinase
EC 2.7.1.21
PF00693 (Herpes_TK)
[Graphical View]

KEGG enzyme name
thymidine kinase
thymidine kinase (phosphorylating)
2'-deoxythymidine kinase
deoxythymidine kinase (phosphorylating)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P03176 KITH_HHV11 ATP + thymidine = ADP + thymidine 5''- phosphate. Homodimer.
P06479 KITH_HHV1S ATP + thymidine = ADP + thymidine 5''- phosphate. Homodimer (By similarity).
P24425 KITH_EHV4 ATP + thymidine = ADP + thymidine 5''- phosphate.
P0C0E6 KITH_VZVO ATP + thymidine = ADP + thymidine 5''- phosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00240 Pyrimidine metabolism
MAP00983 Drug metabolism - other enzymes

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00214 C00008 C00364
E.C.
Compound Magnesium ATP Thymidine ADP Thymidine 5'-phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amide group,nucleoside amine group,nucleotide amide group,nucleotide
ChEBI 18420
18420
15422
15422
17748
17748
16761
16761
17013
17013
PubChem 888
888
5957
5957
5789
5789
6022
6022
9700
9700
1e2hA Unbound Unbound Unbound Unbound Unbound
1e2hB Unbound Unbound Unbound Unbound Unbound
1e2iA Unbound Unbound Analogue:APS-APS-ARP-ARP Unbound Unbound
1e2iB Unbound Unbound Analogue:APS-ARP-APS-ARP Unbound Unbound
1e2jA Unbound Unbound Bound:THM Unbound Unbound
1e2jB Unbound Unbound Bound:THM Unbound Unbound
1e2kA Unbound Unbound Analogue:TMC Unbound Unbound
1e2kB Unbound Unbound Analogue:TMC Unbound Unbound
1e2lA Unbound Unbound Analogue:TMC Unbound Unbound
1e2lB Unbound Unbound Analogue:TMC Unbound Unbound
1e2mA Unbound Unbound Analogue:HPT Unbound Unbound
1e2mB Unbound Unbound Analogue:HPT Unbound Unbound
1e2nA Unbound Unbound Analogue:RCA Unbound Unbound
1e2nB Unbound Unbound Analogue:RCA Unbound Unbound
1e2pA Unbound Unbound Analogue:CCV Unbound Unbound
1e2pB Unbound Unbound Analogue:CCV Unbound Unbound
1ki2A Unbound Unbound Analogue:GA2 Unbound Unbound
1ki2B Unbound Unbound Analogue:GA2 Unbound Unbound
1ki3A Unbound Unbound Analogue:PE2 Unbound Unbound
1ki3B Unbound Unbound Analogue:PE2 Unbound Unbound
1ki4A Unbound Unbound Analogue:BTD Unbound Unbound
1ki4B Unbound Unbound Analogue:BTD Unbound Unbound
1ki5A Unbound Unbound Analogue:AC2 Unbound Unbound
1ki5B Unbound Unbound Unbound Unbound Unbound
1ki6A Unbound Unbound Analogue:AHU Unbound Unbound
1ki6B Unbound Unbound Analogue:AHU Unbound Unbound
1ki7A Unbound Unbound Analogue:ID2 Unbound Unbound
1ki7B Unbound Unbound Analogue:ID2 Unbound Unbound
1ki8A Unbound Unbound Analogue:BVD Unbound Unbound
1ki8B Unbound Unbound Analogue:BVD Unbound Unbound
1kimA Unbound Unbound Bound:THM Unbound Unbound
1kimB Unbound Unbound Bound:THM Unbound Unbound
1kinA Unbound Unbound Bound:THM Unbound Unbound
1kinB Unbound Unbound Bound:THM Unbound Unbound
1of1A Unbound Unbound Analogue:SCT Unbound Unbound
1of1B Unbound Unbound Analogue:SCT Unbound Unbound
1p7cA Unbound Analogue:T5A(ATP) Unbound Unbound Analogue:T5A(TMP)
1p7cB Unbound Unbound Bound:THM Unbound Unbound
1qhiA Unbound Unbound Analogue:BPG Unbound Unbound
1qhiB Unbound Unbound Analogue:BPG Unbound Unbound
1vtkA Unbound Unbound Unbound Bound:ADP Bound:TMP
2ki5A Unbound Unbound Analogue:AC2 Unbound Unbound
2ki5B Unbound Unbound Analogue:AC2 Unbound Unbound
2vtkA Unbound Unbound Bound:THM Bound:ADP Unbound
3vtkA Unbound Unbound Unbound Bound:ADP Analogue:5IU
1osnA Unbound Unbound Unbound Bound:ADP Analogue:BVP
1osnB Unbound Unbound Unbound Bound:ADP Analogue:BVP
1osnC Unbound Unbound Unbound Bound:ADP Analogue:BVP
1osnD Unbound Unbound Unbound Bound:ADP Analogue:BVP
1p6xA Unbound Unbound Bound:THM Unbound Unbound
1p6xB Unbound Unbound Bound:THM Unbound Unbound
1p72A Unbound Unbound Bound:THM Bound:ADP Unbound
1p72B Unbound Unbound Bound:THM Bound:ADP Unbound
1p73A Unbound Analogue:4TA(ATP) Unbound Unbound Analogue:4TA(TMP)
1p73B Unbound Analogue:4TA(ATP) Unbound Unbound Analogue:4TA(TMP)
1p73C Unbound Analogue:4TA(ATP) Unbound Unbound Analogue:4TA(TMP)
1p73D Unbound Analogue:4TA(ATP) Unbound Unbound Analogue:4TA(TMP)
1p75A Unbound Analogue:T5A(ATP) Unbound Unbound Analogue:T5A(TMP)
1p75B Unbound Analogue:T5A(ATP) Unbound Unbound Analogue:T5A(TMP)
1p75C Unbound Analogue:T5A(ATP) Unbound Unbound Analogue:T5A(TMP)
1p75D Unbound Analogue:T5A(ATP) Unbound Unbound Analogue:T5A(TMP)

Reference for Active-site residues
resource references E.C.
litearture [19] & [31]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1e2hA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1e2hB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) invisible 220-225
1e2iA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1e2iB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) invisible 221-224
1e2jA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding) mutant Q125N
1e2jB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) mutant Q125N, invisible 220-225
1e2kA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding) mutant Y101F
1e2kB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) mutant Y101F, invisible 221-224
1e2lA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding) mutant Y101F
1e2lB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) mutant Y101F, invisible 220-225
1e2mA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1e2mB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) invisible 220-225
1e2nA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1e2nB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) invisible 220-226
1e2pA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding) mutant P276S
1e2pB LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) mutant P276S, invisible 220-225
1ki2A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki2B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki3A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki3B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki4A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki4B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki5A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki5B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki6A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki6B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki7A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki7B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki8A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1ki8B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1kimA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1kimB LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1kinA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1kinB LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1of1A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1of1B LYS 62;GLU 83;ARG 163; THR 63;ASP 162(Magnesium binding) invisible 221-223
1p7cA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1p7cB LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1qhiA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1qhiB LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1vtkA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
2ki5A LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
2ki5B LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
2vtkA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
3vtkA LYS 62;GLU 83;ARG 163;ARG 222 THR 63;ASP 162(Magnesium binding)
1osnA LYS 25;GLU 48;ARG 130; THR 26;ASP 129(Magnesium binding) invisible 186-191
1osnB LYS 25;GLU 48;ARG 130; THR 26;ASP 129(Magnesium binding) invisible 186-191
1osnC LYS 25;GLU 48;ARG 130; THR 26;ASP 129(Magnesium binding) invisible 186-191
1osnD LYS 25;GLU 48;ARG 130; THR 26;ASP 129(Magnesium binding) invisible 186-191
1p6xA LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p6xB LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p72A LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p72B LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p73A LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p73B LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p73C LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p73D LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p75A LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding) invisible 199
1p75B LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding)
1p75C LYS 38;GLU 60;ARG 139;ARG 196 SER 39;ASP 138(Magnesium binding) invisible 197-199
1p75D LYS 38;GLU 60;ARG 139; SER 39;ASP 138(Magnesium binding) invisible 195-199

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.290-291
[18]
p.2102-2103
[23]
p.124
[31]
[35]

References
[1]
Resource
Comments
Medline ID
PubMed ID 3003090
Journal J Biol Chem
Year 1986
Volume 261
Pages 1985-7
Authors Arnold JR, Cheng MS, Cullis PM, Lowe G
Title The stereochemical course of phosphoryl transfer catalyzed by herpes simplex virus type I-induced thymidine kinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Medline ID
PubMed ID 3007662
Journal J Gen Virol
Year 1986
Volume 67
Pages 753-8
Authors Graham D, Larder BA, Inglis MM
Title Evidence that the 'active centre' of the herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide.
Related PDB
Related UniProtKB P06479
[3]
Resource
Comments
Medline ID
PubMed ID 3588286
Journal Nucleic Acids Res
Year 1987
Volume 15
Pages 4111-21
Authors Parkanyi L, Kalman A, Czugler M, Kovacs T, Walker RT
Title A comparison of the conformations adopted by some 5-bromovinyl-2'-deoxyuridines and a correlation with their antiviral properties: an X-ray study.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8218229
Journal Biochemistry
Year 1993
Volume 32
Pages 11618-26
Authors Black ME, Loeb LA
Title Identification of important residues within the putative nucleoside binding site of HSV-1 thymidine kinase by random sequence selection: analysis of selected mutants in vitro.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8396286
Journal Virus Genes
Year 1993
Volume 7
Pages 205-9
Authors Fetzer J, Folkers G, Muller I, Keil GM
Title Site-directed mutagenesis in the active site of the herpes simplex virus type 1 thymidine kinase gene.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7993074
Journal Antiviral Res
Year 1994
Volume 24
Pages 289-304
Authors Olivier A, Creuven I, Evrard C, Evrard G, Dory M, van Aerschot A, Wigerinck P, Herdewijn P, Durant F
Title Stereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8068016
Journal Biochem J
Year 1994
Volume 302
Pages 279-82
Authors Maga G, Focher F, Wright GE, Capobianco M, Garbesi A, Bendiscioli A, Spadari S
Title Kinetic studies with N2-phenylguanines and with L-thymidine indicate that herpes simplex virus type-1 thymidine kinase and thymidylate kinase share a common active site.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 7957251
Journal Eur J Biochem
Year 1994
Volume 226
Pages 219-26
Authors Michael M, Fetzer J, Folkers G
Title Site-directed mutagenesis clarifies the substrate position within the three-dimensional model of the active site of herpes simplex virus type-1 thymidine kinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7733991
Journal Biochem Biophys Res Commun
Year 1995
Volume 209
Pages 966-73
Authors Michael M, Fetzer J, Folkers G
Title Site-directed mutagenesis of herpes simplex virus type 1 thymidine kinase opposes the importance of amino acid positions 251, 321 and 348 for selective recognition of substrate analogs.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-376.
Medline ID
PubMed ID 7628623
Journal FEBS Lett
Year 1995
Volume 368
Pages 289-92
Authors Wild K, Bohner T, Aubry A, Folkers G, Schulz GE
Title The three-dimensional structure of thymidine kinase from herpes simplex virus type 1.
Related PDB
Related UniProtKB P03176
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID
PubMed ID 7552712
Journal Nat Struct Biol
Year 1995
Volume 2
Pages 876-81
Authors Brown DG, Visse R, Sandhu G, Davies A, Rizkallah PJ, Melitz C, Summers WC, Sanderson MR
Title Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir.
Related PDB 1kin
Related UniProtKB P03176
[12]
Resource
Comments
Medline ID
PubMed ID 8660548
Journal Anal Biochem
Year 1996
Volume 237
Pages 135-40
Authors Rechtin TM, Black ME, Drake RR
Title Proteolytic mapping of the thymidine/thymidylate binding site of herpes simplex virus type 1 thymidine kinase: a general photoaffinity labeling method for identifying active-site peptides.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8783799
Journal Antiviral Res
Year 1996
Volume 30
Pages 63-74
Authors Creuven I, Evrard C, Olivier A, Evrard G, Van Aerschot A, Wigerinck P, Herdewijn P, Durant F
Title Relationship between structural properties and affinity for herpes simplex virus type 1 thymidine kinase of bromine substituted 5-heteroaromatic 2'-deoxyuridines.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8941385
Journal J Med Chem
Year 1996
Volume 39
Pages 4727-37
Authors De Winter H, Herdewijn P
Title Understanding the binding of 5-substituted 2'-deoxyuridine substrates to thymidine kinase of herpes simplex virus type-1.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8622970
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 3525-9
Authors Black ME, Newcomb TG, Wilson HM, Loeb LA
Title Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9450049
Journal Biochem Soc Trans
Year 1997
Volume 25
Pages S621
Authors Evans JS, Lock KP, Levine BA, Champness JN, Sanderson MR, Summers WC, Buchan A
Title Structure-specificity features of HSV-1 thymidine kinases.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9029509
Journal J Recept Signal Transduct Res
Year 1997
Volume 17
Pages 475-94
Authors Folkers G, Alber F, Amrhein I, Behrends H, Bohner T, Gerber S, Kuonen O, Scapozza L
Title Integrated homology modelling and X-ray study of herpes simplex virus I thymidine kinase: a case study.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-376.
Medline ID
PubMed ID 9336833
Journal Protein Sci
Year 1997
Volume 6
Pages 2097-106
Authors Wild K, Bohner T, Folkers G, Schulz GE
Title The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.
Related PDB 1vtk 2vtk 3vtk
Related UniProtKB P03176
[19]
Resource
Comments
Medline ID
PubMed ID 9716390
Journal Eur J Biochem
Year 1998
Volume 255
Pages 472-81
Authors Kussmann-Gerber S, Kuonen O, Folkers G, Pilger BD, Scapozza L
Title Drug resistance of herpes simplex virus type 1--structural considerations at the molecular level of the thymidine kinase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9747715
Journal J Gen Virol
Year 1998
Volume 79
Pages 2083-92
Authors Evans JS, Lock KP, Levine BA, Champness JN, Sanderson MR, Summers WC, McLeish PJ, Buchan A
Title Herpesviral thymidine kinases: laxity and resistance by design.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID
PubMed ID 9715911
Journal Proteins
Year 1998
Volume 32
Pages 350-61
Authors Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR
Title Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands.
Related PDB 1ki2 1ki3 1ki4 1ki5 1ki6 1ki7 1ki8 1kim
Related UniProtKB P03176
[22]
Resource
Comments
Medline ID
PubMed ID 10386936
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 1563-6
Authors Wouters J, Herdewijn P
Title 5-Substituted pyrimidine 1,5-anhydrohexitols: conformational analysis and interaction with viral thymidine kinase.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID
PubMed ID 9989588
Journal FEBS Lett
Year 1999
Volume 443
Pages 121-5
Authors Bennett MS, Wien F, Champness JN, Batuwangala T, Rutherford T, Summers WC, Sun H, Wright G, Sanderson MR
Title Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir.
Related PDB 1qhi 2ki5
Related UniProtKB P03176
[24]
Resource
Comments
Medline ID
PubMed ID 10542226
Journal J Biol Chem
Year 1999
Volume 274
Pages 31967-73
Authors Pilger BD, Perozzo R, Alber F, Wurth C, Folkers G, Scapozza L
Title Substrate diversity of herpes simplex virus thymidine kinase. Impact Of the kinematics of the enzyme.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10358938
Journal Nucleosides Nucleotides
Year 1999
Volume 18
Pages 311-30
Authors Kussmann-Gerber S, Wurth C, Scapozza L, Pilger BD, Pliska V, Folkers G
Title Interaction of the recombinant herpes simplex virus type 1 thymidine kinase with thymidine and aciclovir: a kinetic study.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10747801
Journal Biochemistry
Year 2000
Volume 39
Pages 4105-11
Authors Hinds TA, Compadre C, Hurlburt BK, Drake RR
Title Conservative mutations of glutamine-125 in herpes simplex virus type 1 thymidine kinase result in a ganciclovir kinase with minimal deoxypyrimidine kinase activities.
Related PDB
Related UniProtKB
[27]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10924157
Journal Biochemistry
Year 2000
Volume 39
Pages 9597-603
Authors Prota A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G, Scapozza L
Title Kinetics and crystal structure of the wild-type and the engineered Y101F mutant of Herpes simplex virus type 1 thymidine kinase interacting with (North)-methanocarba-thymidine.
Related PDB 1e2k 1e2l
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 10747922
Journal J Biol Chem
Year 2000
Volume 275
Pages 16139-45
Authors Perozzo R, Jelesarov I, Bosshard HR, Folkers G, Scapozza L
Title Compulsory order of substrate binding to herpes simplex virus type 1 thymidine kinase. A calorimetric study.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 10935205
Journal J Mol Graph Model
Year 2000
Volume 18
Pages 33-41
Authors Gaudio AC, Richards WG, Takahata Y
Title QSAR and molecular graphics analysis of N2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.
Related PDB
Related UniProtKB
[30]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11056041
Journal Proteins
Year 2000
Volume 41
Pages 545-53
Authors Vogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, Folkers G, Scapozza L, Schulz GE
Title Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography.
Related PDB 1e2h 1e2i 1e2j
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11262392
Journal J Biol Chem
Year 2001
Volume 276
Pages 21692-7
Authors Sulpizi M, Schelling P, Folkers G, Carloni P, Scapozza L
Title The rational of catalytic activity of herpes simplex virus thymidine kinase. a combined biochemical and quantum chemical study.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11676546
Journal J Mol Biol
Year 2001
Volume 313
Pages 657-70
Authors Wurth C, Thomas RM, Folkers G, Scapozza L
Title Folding and self-assembly of herpes simplex virus type 1 thymidine kinase.
Related PDB
Related UniProtKB
[33]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11266595
Journal Protein Sci
Year 2001
Volume 10
Pages 63-73
Authors Wurth C, Kessler U, Vogt J, Schulz GE, Folkers G, Scapozza L
Title The effect of substrate binding on the conformation and structural stability of Herpes simplex virus type 1 thymidine kinase.
Related PDB 1e2m 1e2n 1e2p
Related UniProtKB
[34]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12686543
Journal J Biol Chem
Year 2003
Volume 278
Pages 24680-7
Authors Bird LE, Ren J, Wright A, Leslie KD, Degreve B, Balzarini J, Stammers DK
Title Crystal structure of varicella zoster virus thymidine kinase.
Related PDB 1osn
Related UniProtKB
[35]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 14527394
Journal Structure (Camb)
Year 2003
Volume 11
Pages 1265-77
Authors Gardberg A, Shuvalova L, Monnerjahn C, Konrad M, Lavie A
Title Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.
Related PDB 1p7c 1p6x 1p72 1p73 1p75
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 14705959
Journal Biochem J
Year 2004
Volume 379
Pages 795-803
Authors Wu CC, Chen MC, Chang YR, Hsu TY, Chen JY
Title Identification and characterization of the conserved nucleoside-binding sites in the Epstein-Barr virus thymidine kinase.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 14719951
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 543-9
Authors Marquez VE, Ben-Kasus T, Barchi JJ Jr, Green KM, Nicklaus MC, Agbaria R
Title Experimental and structural evidence that herpes 1 kinase and cellular DNA polymerase(s) discriminate on the basis of sugar pucker.
Related PDB
Related UniProtKB
[38]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15163659
Journal J Biol Chem
Year 2004
Volume 279
Pages 32832-8
Authors Schelling P, Claus MT, Johner R, Marquez VE, Schulz GE, Scapozza L
Title Biochemical and structural characterization of (South)-methanocarbathymidine that specifically inhibits growth of herpes simplex virus type 1 thymidine kinase-transduced osteosarcoma cells.
Related PDB 1of1
Related UniProtKB

Comments
Although there has been no structure with magnesium ion bound to the active site, this enzyme should bind a magnesium ion as cofactor to the sidechains of Thr63 and Asp162 (of PDB;1e2h).
The catalytic mechanism proceeds as follows:
(1) Glu83 acts as a general base to activate the acceptor group, 5'-hydroxyl group of thymidine.
(2) The activated acceptor group makes a nucleophilic attack on the transferred group, gamma-phosphate of ATP.
(3) During the transition state, the transferred group and leaving group (beta- and alpha-phosphate groups of ATP) must be stabilized by stabilizer residues, Arg/Lys cluster, along with the magnesium ion as cofactor.

Created Updated
2002-05-31 2009-02-26