EzCatDB: S00302

DB codeS00302
RLCP classification3.103.70000.350
CATH domainDomain 13.40.50.300Catalytic domain
E.C.2.7.1.21
CSA1kim

CATH domainRelated DB codes (homologues)
3.40.50.300S00527,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

Enzyme Name
Swiss-protKEGG

P03176P06479P24425P0C0E6
Protein nameThymidine kinaseThymidine kinaseThymidine kinaseThymidine kinasethymidine kinase
thymidine kinase (phosphorylating)
2'-deoxythymidine kinase
deoxythymidine kinase (phosphorylating)
SynonymsEC 2.7.1.21
EC 2.7.1.21
EC 2.7.1.21
EC 2.7.1.21

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism
MAP00983Drug metabolism - other enzymes

Swiss-prot:Accession NumberP03176P06479P24425P0C0E6
Entry nameKITH_HHV11KITH_HHV1SKITH_EHV4KITH_VZVO
ActivityATP + thymidine = ADP + thymidine 5''- phosphate.ATP + thymidine = ADP + thymidine 5''- phosphate.ATP + thymidine = ADP + thymidine 5''- phosphate.ATP + thymidine = ADP + thymidine 5''- phosphate.
SubunitHomodimer.Homodimer (By similarity).

Subcellular location



Cofactor





CofactorsSubstratesProducts
KEGG-idC00305C00002C00214C00008C00364
CompoundMagnesiumATPThymidineADPThymidine 5'-phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamide group,nucleosideamine group,nucleotideamide group,nucleotide
1e2hAUnboundUnboundUnboundUnboundUnbound
1e2hBUnboundUnboundUnboundUnboundUnbound
1e2iAUnboundUnboundAnalogue:APS-APS-ARP-ARPUnboundUnbound
1e2iBUnboundUnboundAnalogue:APS-ARP-APS-ARPUnboundUnbound
1e2jAUnboundUnboundBound:THMUnboundUnbound
1e2jBUnboundUnboundBound:THMUnboundUnbound
1e2kAUnboundUnboundAnalogue:TMCUnboundUnbound
1e2kBUnboundUnboundAnalogue:TMCUnboundUnbound
1e2lAUnboundUnboundAnalogue:TMCUnboundUnbound
1e2lBUnboundUnboundAnalogue:TMCUnboundUnbound
1e2mAUnboundUnboundAnalogue:HPTUnboundUnbound
1e2mBUnboundUnboundAnalogue:HPTUnboundUnbound
1e2nAUnboundUnboundAnalogue:RCAUnboundUnbound
1e2nBUnboundUnboundAnalogue:RCAUnboundUnbound
1e2pAUnboundUnboundAnalogue:CCVUnboundUnbound
1e2pBUnboundUnboundAnalogue:CCVUnboundUnbound
1ki2AUnboundUnboundAnalogue:GA2UnboundUnbound
1ki2BUnboundUnboundAnalogue:GA2UnboundUnbound
1ki3AUnboundUnboundAnalogue:PE2UnboundUnbound
1ki3BUnboundUnboundAnalogue:PE2UnboundUnbound
1ki4AUnboundUnboundAnalogue:BTDUnboundUnbound
1ki4BUnboundUnboundAnalogue:BTDUnboundUnbound
1ki5AUnboundUnboundAnalogue:AC2UnboundUnbound
1ki5BUnboundUnboundUnboundUnboundUnbound
1ki6AUnboundUnboundAnalogue:AHUUnboundUnbound
1ki6BUnboundUnboundAnalogue:AHUUnboundUnbound
1ki7AUnboundUnboundAnalogue:ID2UnboundUnbound
1ki7BUnboundUnboundAnalogue:ID2UnboundUnbound
1ki8AUnboundUnboundAnalogue:BVDUnboundUnbound
1ki8BUnboundUnboundAnalogue:BVDUnboundUnbound
1kimAUnboundUnboundBound:THMUnboundUnbound
1kimBUnboundUnboundBound:THMUnboundUnbound
1kinAUnboundUnboundBound:THMUnboundUnbound
1kinBUnboundUnboundBound:THMUnboundUnbound
1of1AUnboundUnboundAnalogue:SCTUnboundUnbound
1of1BUnboundUnboundAnalogue:SCTUnboundUnbound
1p7cAUnboundAnalogue:T5A(ATP)UnboundUnboundAnalogue:T5A(TMP)
1p7cBUnboundUnboundBound:THMUnboundUnbound
1qhiAUnboundUnboundAnalogue:BPGUnboundUnbound
1qhiBUnboundUnboundAnalogue:BPGUnboundUnbound
1vtkAUnboundUnboundUnboundBound:ADPBound:TMP
2ki5AUnboundUnboundAnalogue:AC2UnboundUnbound
2ki5BUnboundUnboundAnalogue:AC2UnboundUnbound
2vtkAUnboundUnboundBound:THMBound:ADPUnbound
3vtkAUnboundUnboundUnboundBound:ADPAnalogue:5IU
1osnAUnboundUnboundUnboundBound:ADPAnalogue:BVP
1osnBUnboundUnboundUnboundBound:ADPAnalogue:BVP
1osnCUnboundUnboundUnboundBound:ADPAnalogue:BVP
1osnDUnboundUnboundUnboundBound:ADPAnalogue:BVP
1p6xAUnboundUnboundBound:THMUnboundUnbound
1p6xBUnboundUnboundBound:THMUnboundUnbound
1p72AUnboundUnboundBound:THMBound:ADPUnbound
1p72BUnboundUnboundBound:THMBound:ADPUnbound
1p73AUnboundAnalogue:4TA(ATP)UnboundUnboundAnalogue:4TA(TMP)
1p73BUnboundAnalogue:4TA(ATP)UnboundUnboundAnalogue:4TA(TMP)
1p73CUnboundAnalogue:4TA(ATP)UnboundUnboundAnalogue:4TA(TMP)
1p73DUnboundAnalogue:4TA(ATP)UnboundUnboundAnalogue:4TA(TMP)
1p75AUnboundAnalogue:T5A(ATP)UnboundUnboundAnalogue:T5A(TMP)
1p75BUnboundAnalogue:T5A(ATP)UnboundUnboundAnalogue:T5A(TMP)
1p75CUnboundAnalogue:T5A(ATP)UnboundUnboundAnalogue:T5A(TMP)
1p75DUnboundAnalogue:T5A(ATP)UnboundUnboundAnalogue:T5A(TMP)

Active-site residues
resource
litearture [19] & [31]
pdbCatalytic residuesCofactor-binding residuescomment
1e2hALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1e2hBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
invisible 220-225
1e2iALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1e2iBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
invisible 221-224
1e2jALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)
mutant Q125N
1e2jBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
mutant Q125N, invisible 220-225
1e2kALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)
mutant Y101F
1e2kBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
mutant Y101F, invisible 221-224
1e2lALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)
mutant Y101F
1e2lBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
mutant Y101F, invisible 220-225
1e2mALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1e2mBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
invisible 220-225
1e2nALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1e2nBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
invisible 220-226
1e2pALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)
mutant P276S
1e2pBLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
mutant P276S, invisible 220-225
1ki2ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki2BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki3ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki3BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki4ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki4BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki5ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki5BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki6ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki6BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki7ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki7BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki8ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1ki8BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1kimALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1kimBLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1kinALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1kinBLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1of1ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1of1BLYS 62;GLU 83;ARG 163;       
THR 63;ASP 162(Magnesium binding)
invisible 221-223
1p7cALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1p7cBLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1qhiALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1qhiBLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1vtkALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

2ki5ALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

2ki5BLYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

2vtkALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

3vtkALYS 62;GLU 83;ARG 163;ARG 222
THR 63;ASP 162(Magnesium binding)

1osnALYS 25;GLU 48;ARG 130;       
THR 26;ASP 129(Magnesium binding)
invisible 186-191
1osnBLYS 25;GLU 48;ARG 130;       
THR 26;ASP 129(Magnesium binding)
invisible 186-191
1osnCLYS 25;GLU 48;ARG 130;       
THR 26;ASP 129(Magnesium binding)
invisible 186-191
1osnDLYS 25;GLU 48;ARG 130;       
THR 26;ASP 129(Magnesium binding)
invisible 186-191
1p6xALYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p6xBLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p72ALYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p72BLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p73ALYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p73BLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p73CLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p73DLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p75ALYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)
invisible 199
1p75BLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)

1p75CLYS 38;GLU 60;ARG 139;ARG 196
SER 39;ASP 138(Magnesium binding)
invisible 197-199
1p75DLYS 38;GLU 60;ARG 139;       
SER 39;ASP 138(Magnesium binding)
invisible 195-199

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.290-291
[18]p.2102-2103
[23]p.124
[31]

[35]


references
[1]
PubMed ID3003090
JournalJ Biol Chem
Year1986
Volume261
Pages1985-7
AuthorsArnold JR, Cheng MS, Cullis PM, Lowe G
TitleThe stereochemical course of phosphoryl transfer catalyzed by herpes simplex virus type I-induced thymidine kinase.
[2]
CommentsNUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed ID3007662
JournalJ Gen Virol
Year1986
Volume67
Pages753-8
AuthorsGraham D, Larder BA, Inglis MM
TitleEvidence that the 'active centre' of the herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide.
Related Swiss-protP06479
[3]
PubMed ID3588286
JournalNucleic Acids Res
Year1987
Volume15
Pages4111-21
AuthorsParkanyi L, Kalman A, Czugler M, Kovacs T, Walker RT
TitleA comparison of the conformations adopted by some 5-bromovinyl-2'-deoxyuridines and a correlation with their antiviral properties: an X-ray study.
[4]
PubMed ID8218229
JournalBiochemistry
Year1993
Volume32
Pages11618-26
AuthorsBlack ME, Loeb LA
TitleIdentification of important residues within the putative nucleoside binding site of HSV-1 thymidine kinase by random sequence selection: analysis of selected mutants in vitro.
[5]
PubMed ID8396286
JournalVirus Genes
Year1993
Volume7
Pages205-9
AuthorsFetzer J, Folkers G, Muller I, Keil GM
TitleSite-directed mutagenesis in the active site of the herpes simplex virus type 1 thymidine kinase gene.
[6]
PubMed ID7993074
JournalAntiviral Res
Year1994
Volume24
Pages289-304
AuthorsOlivier A, Creuven I, Evrard C, Evrard G, Dory M, van Aerschot A, Wigerinck P, Herdewijn P, Durant F
TitleStereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU.
[7]
PubMed ID8068016
JournalBiochem J
Year1994
Volume302
Pages279-82
AuthorsMaga G, Focher F, Wright GE, Capobianco M, Garbesi A, Bendiscioli A, Spadari S
TitleKinetic 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.
[8]
PubMed ID7957251
JournalEur J Biochem
Year1994
Volume226
Pages219-26
AuthorsMichael M, Fetzer J, Folkers G
TitleSite-directed mutagenesis clarifies the substrate position within the three-dimensional model of the active site of herpes simplex virus type-1 thymidine kinase.
[9]
PubMed ID7733991
JournalBiochem Biophys Res Commun
Year1995
Volume209
Pages966-73
AuthorsMichael M, Fetzer J, Folkers G
TitleSite-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.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-376.
PubMed ID7628623
JournalFEBS Lett
Year1995
Volume368
Pages289-92
AuthorsWild K, Bohner T, Aubry A, Folkers G, Schulz GE
TitleThe three-dimensional structure of thymidine kinase from herpes simplex virus type 1.
Related Swiss-protP03176
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
PubMed ID7552712
JournalNat Struct Biol
Year1995
Volume2
Pages876-81
AuthorsBrown DG, Visse R, Sandhu G, Davies A, Rizkallah PJ, Melitz C, Summers WC, Sanderson MR
TitleCrystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir.
Related PDB1kin
Related Swiss-protP03176
[12]
PubMed ID8660548
JournalAnal Biochem
Year1996
Volume237
Pages135-40
AuthorsRechtin TM, Black ME, Drake RR
TitleProteolytic 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.
[13]
PubMed ID8783799
JournalAntiviral Res
Year1996
Volume30
Pages63-74
AuthorsCreuven I, Evrard C, Olivier A, Evrard G, Van Aerschot A, Wigerinck P, Herdewijn P, Durant F
TitleRelationship between structural properties and affinity for herpes simplex virus type 1 thymidine kinase of bromine substituted 5-heteroaromatic 2'-deoxyuridines.
[14]
PubMed ID8941385
JournalJ Med Chem
Year1996
Volume39
Pages4727-37
AuthorsDe Winter H, Herdewijn P
TitleUnderstanding the binding of 5-substituted 2'-deoxyuridine substrates to thymidine kinase of herpes simplex virus type-1.
[15]
PubMed ID8622970
JournalProc Natl Acad Sci U S A
Year1996
Volume93
Pages3525-9
AuthorsBlack ME, Newcomb TG, Wilson HM, Loeb LA
TitleCreation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy.
[16]
PubMed ID9450049
JournalBiochem Soc Trans
Year1997
Volume25
PagesS621
AuthorsEvans JS, Lock KP, Levine BA, Champness JN, Sanderson MR, Summers WC, Buchan A
TitleStructure-specificity features of HSV-1 thymidine kinases.
[17]
PubMed ID9029509
JournalJ Recept Signal Transduct Res
Year1997
Volume17
Pages475-94
AuthorsFolkers G, Alber F, Amrhein I, Behrends H, Bohner T, Gerber S, Kuonen O, Scapozza L
TitleIntegrated homology modelling and X-ray study of herpes simplex virus I thymidine kinase: a case study.
[18]
CommentsX-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-376.
PubMed ID9336833
JournalProtein Sci
Year1997
Volume6
Pages2097-106
AuthorsWild K, Bohner T, Folkers G, Schulz GE
TitleThe structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.
Related PDB1vtk,2vtk,3vtk
Related Swiss-protP03176
[19]
PubMed ID9716390
JournalEur J Biochem
Year1998
Volume255
Pages472-81
AuthorsKussmann-Gerber S, Kuonen O, Folkers G, Pilger BD, Scapozza L
TitleDrug resistance of herpes simplex virus type 1--structural considerations at the molecular level of the thymidine kinase.
[20]
PubMed ID9747715
JournalJ Gen Virol
Year1998
Volume79
Pages2083-92
AuthorsEvans JS, Lock KP, Levine BA, Champness JN, Sanderson MR, Summers WC, McLeish PJ, Buchan A
TitleHerpesviral thymidine kinases: laxity and resistance by design.
[21]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
PubMed ID9715911
JournalProteins
Year1998
Volume32
Pages350-61
AuthorsChampness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR
TitleExploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands.
Related PDB1ki2,1ki3,1ki4,1ki5,1ki6,1ki7,1ki8,1kim
Related Swiss-protP03176
[22]
PubMed ID10386936
JournalBioorg Med Chem Lett
Year1999
Volume9
Pages1563-6
AuthorsWouters J, Herdewijn P
Title5-Substituted pyrimidine 1,5-anhydrohexitols: conformational analysis and interaction with viral thymidine kinase.
[23]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
PubMed ID9989588
JournalFEBS Lett
Year1999
Volume443
Pages121-5
AuthorsBennett MS, Wien F, Champness JN, Batuwangala T, Rutherford T, Summers WC, Sun H, Wright G, Sanderson MR
TitleStructure 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 PDB1qhi,2ki5
Related Swiss-protP03176
[24]
PubMed ID10542226
JournalJ Biol Chem
Year1999
Volume274
Pages31967-73
AuthorsPilger BD, Perozzo R, Alber F, Wurth C, Folkers G, Scapozza L
TitleSubstrate diversity of herpes simplex virus thymidine kinase. Impact Of the kinematics of the enzyme.
[25]
PubMed ID10358938
JournalNucleosides Nucleotides
Year1999
Volume18
Pages311-30
AuthorsKussmann-Gerber S, Wurth C, Scapozza L, Pilger BD, Pliska V, Folkers G
TitleInteraction of the recombinant herpes simplex virus type 1 thymidine kinase with thymidine and aciclovir: a kinetic study.
[26]
PubMed ID10747801
JournalBiochemistry
Year2000
Volume39
Pages4105-11
AuthorsHinds TA, Compadre C, Hurlburt BK, Drake RR
TitleConservative mutations of glutamine-125 in herpes simplex virus type 1 thymidine kinase result in a ganciclovir kinase with minimal deoxypyrimidine kinase activities.
[27]
CommentsX-ray crystallography
PubMed ID10924157
JournalBiochemistry
Year2000
Volume39
Pages9597-603
AuthorsProta A, Vogt J, Pilger B, Perozzo R, Wurth C, Marquez VE, Russ P, Schulz GE, Folkers G, Scapozza L
TitleKinetics 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 PDB1e2k,1e2l
[28]
PubMed ID10747922
JournalJ Biol Chem
Year2000
Volume275
Pages16139-45
AuthorsPerozzo R, Jelesarov I, Bosshard HR, Folkers G, Scapozza L
TitleCompulsory order of substrate binding to herpes simplex virus type 1 thymidine kinase. A calorimetric study.
[29]
PubMed ID10935205
JournalJ Mol Graph Model
Year2000
Volume18
Pages33-41
AuthorsGaudio AC, Richards WG, Takahata Y
TitleQSAR and molecular graphics analysis of N2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.
[30]
CommentsX-ray crystallography
PubMed ID11056041
JournalProteins
Year2000
Volume41
Pages545-53
AuthorsVogt J, Perozzo R, Pautsch A, Prota A, Schelling P, Pilger B, Folkers G, Scapozza L, Schulz GE
TitleNucleoside binding site of herpes simplex type 1 thymidine kinase analyzed by X-ray crystallography.
Related PDB1e2h,1e2i,1e2j
[31]
PubMed ID11262392
JournalJ Biol Chem
Year2001
Volume276
Pages21692-7
AuthorsSulpizi M, Schelling P, Folkers G, Carloni P, Scapozza L
TitleThe rational of catalytic activity of herpes simplex virus thymidine kinase. a combined biochemical and quantum chemical study.
[32]
PubMed ID11676546
JournalJ Mol Biol
Year2001
Volume313
Pages657-70
AuthorsWurth C, Thomas RM, Folkers G, Scapozza L
TitleFolding and self-assembly of herpes simplex virus type 1 thymidine kinase.
[33]
CommentsX-ray crystallography
PubMed ID11266595
JournalProtein Sci
Year2001
Volume10
Pages63-73
AuthorsWurth C, Kessler U, Vogt J, Schulz GE, Folkers G, Scapozza L
TitleThe effect of substrate binding on the conformation and structural stability of Herpes simplex virus type 1 thymidine kinase.
Related PDB1e2m,1e2n,1e2p
[34]
CommentsX-ray crystallography
PubMed ID12686543
JournalJ Biol Chem
Year2003
Volume278
Pages24680-7
AuthorsBird LE, Ren J, Wright A, Leslie KD, Degreve B, Balzarini J, Stammers DK
TitleCrystal structure of varicella zoster virus thymidine kinase.
Related PDB1osn
[35]
CommentsX-ray crystallography
PubMed ID14527394
JournalStructure (Camb)
Year2003
Volume11
Pages1265-77
AuthorsGardberg A, Shuvalova L, Monnerjahn C, Konrad M, Lavie A
TitleStructural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.
Related PDB1p7c,1p6x,1p72,1p73,1p75
[36]
PubMed ID14705959
JournalBiochem J
Year2004
Volume379
Pages795-803
AuthorsWu CC, Chen MC, Chang YR, Hsu TY, Chen JY
TitleIdentification and characterization of the conserved nucleoside-binding sites in the Epstein-Barr virus thymidine kinase.
[37]
PubMed ID14719951
JournalJ Am Chem Soc
Year2004
Volume126
Pages543-9
AuthorsMarquez VE, Ben-Kasus T, Barchi JJ Jr, Green KM, Nicklaus MC, Agbaria R
TitleExperimental and structural evidence that herpes 1 kinase and cellular DNA polymerase(s) discriminate on the basis of sugar pucker.
[38]
CommentsX-ray crystallography
PubMed ID15163659
JournalJ Biol Chem
Year2004
Volume279
Pages32832-8
AuthorsSchelling P, Claus MT, Johner R, Marquez VE, Schulz GE, Scapozza L
TitleBiochemical and structural characterization of (South)-methanocarbathymidine that specifically inhibits growth of herpes simplex virus type 1 thymidine kinase-transduced osteosarcoma cells.
Related PDB1of1

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.

createdupdated
2002-05-312009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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