EzCatDB: S00682
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DB codeS00682
RLCP classification3.103.69910.364 : Transfer
CATH domainDomain 13.40.50.300 : Rossmann foldCatalytic domain
E.C.2.7.1.74

CATH domainRelated DB codes (homologues)
3.40.50.300 : Rossmann foldS00527,S00547,S00548,S00550,S00554,S00555,S00671,S00672,S00676,S00680,S00913,S00914,S00301,S00302,S00303,S00304,S00307,S00308,S00305,S00306,S00309,S00310,S00311,M00114,M00199,D00129,D00130,D00540,M00186

Enzyme Name
UniProtKBKEGG

P27707
Protein nameDeoxycytidine kinaseDeoxycytidine kinase
Deoxycytidine kinase (phosphorylating)
2'-Deoxycytidine kinase
Ara-C kinase
Arabinofuranosylcytosine kinase
Deoxycytidine-cytidine kinase
SynonymsdCK
EC 2.7.1.74
RefSeqNP_000779.1 (Protein)
NM_000788.2 (DNA/RNA sequence)
PfamPF01712 (dNK)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism
MAP00240Pyrimidine metabolism

UniProtKB:Accession NumberP27707
Entry nameDCK_HUMAN
ActivityNTP + deoxycytidine = NDP + dCMP.
SubunitHomodimer.
Subcellular locationNucleus.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00201C00881C00454C00239
CompoundMagnesiumNTPdeoxycytidineNDPdCMP
Typedivalent metal (Ca2+, Mg2+)nucleotideamine group,nucleosidenucleotideamine group,nucleotide
ChEBI18420

15698

15918
PubChem888

13711

13945
             
1p5zB00Bound:_MGUnboundAnalogue:AR3Bound:ADPUnbound
1p60A00UnboundUnboundBound:DCZBound:ADPUnbound
1p60B00UnboundUnboundBound:DCZBound:ADPUnbound
1p61B00UnboundUnboundBound:DCZBound:ADPUnbound
1p62B00Bound:_MGUnboundAnalogue:GEOBound:ADPUnbound
2a2zA00Bound:_MGUnboundBound:DCZBound:UDPUnbound
2a2zB00Bound:_MGUnboundBound:DCZBound:UDPUnbound
2a2zC00Bound:_MGUnboundBound:DCZBound:UDPUnbound
2a2zD00Bound:_MGUnboundBound:DCZBound:UDPUnbound
2a30A00UnboundUnboundBound:DCZUnboundUnbound
2a30B00UnboundUnboundBound:DCZUnboundUnbound
2a30C00UnboundUnboundBound:DCZUnboundUnbound
2a30D00UnboundUnboundBound:DCZUnboundUnbound
2a7qA00Bound:_MGUnboundAnalogue:CFBBound:ADPUnbound
2no0A00UnboundUnboundAnalogue:GEOBound:ADPUnbound
2no0B00UnboundUnboundAnalogue:GEOBound:ADPUnbound
2no1A00UnboundUnboundBound:DCZBound:ADPUnbound
2no1B00UnboundUnboundBound:DCZBound:ADPUnbound
2no6A00UnboundUnboundAnalogue:ETVBound:ADPUnbound
2no6B00UnboundUnboundAnalogue:ETVBound:ADPUnbound
2no7A00UnboundUnboundAnalogue:LDCBound:ADPUnbound
2no7B00UnboundUnboundAnalogue:LDCBound:ADPUnbound
2no9A00UnboundUnboundAnalogue:LTTBound:ADPUnbound
2no9B00UnboundUnboundAnalogue:LTTBound:ADPUnbound
2noaA00UnboundUnboundAnalogue:3TCBound:ADPUnbound
2noaB00UnboundUnboundAnalogue:3TCBound:ADPUnbound
2qrnA00Bound:_MGUnboundUnboundBound:UDPBound:DCM
2qrnB00Bound:_MGUnboundUnboundBound:UDPBound:DCM
2qrnC00Bound:_MGUnboundUnboundBound:UDPBound:DCM
2qrnD00Bound:_MGUnboundUnboundBound:UDPBound:DCM
2qroA00Bound:_MGUnboundUnboundBound:UDPAnalogue:D5M
2qroB00Bound:_MGUnboundUnboundBound:UDPAnalogue:D5M
2qroC00Bound:_MGUnboundUnboundBound:UDPAnalogue:D5M
2qroD00Bound:_MGUnboundUnboundBound:UDPAnalogue:D5M
2zi3A00UnboundUnboundAnalogue:3D1Bound:ADPUnbound
2zi3B00UnboundUnboundAnalogue:3D1Bound:ADPUnbound
2zi4A00Bound:_MGUnboundAnalogue:3L1Bound:ADPUnbound
2zi5A00UnboundUnboundAnalogue:3L1Bound:UDPUnbound
2zi5B00UnboundUnboundAnalogue:3L1Bound:UDPUnbound
2zi5C00UnboundUnboundAnalogue:3L1Bound:UDPUnbound
2zi5D00UnboundUnboundAnalogue:3L1Bound:UDPUnbound
2zi6A00UnboundUnboundAnalogue:3D1Bound:UDPUnbound
2zi6B00UnboundUnboundAnalogue:3D1Bound:UDPUnbound
2zi6C00UnboundUnboundAnalogue:3D1Bound:UDPUnbound
2zi6D00UnboundUnboundAnalogue:3D1Bound:UDPUnbound
2zi7A00UnboundUnboundAnalogue:GNGBound:UDPUnbound
2zi7B00UnboundUnboundAnalogue:GNGBound:UDPUnbound
2zi9A00UnboundUnboundAnalogue:CL9Bound:ADPUnbound
2zi9B00UnboundUnboundAnalogue:CL9Bound:ADPUnbound
2ziaA00UnboundUnboundAnalogue:CL9Bound:UDPUnbound
2ziaB00UnboundUnboundAnalogue:CL9Bound:UDPUnbound
3exkA00UnboundUnboundAnalogue:THMBound:ADPUnbound
3hp1A00UnboundUnboundAnalogue:LLTBound:ADPUnbound
3ipxA00Bound:_MGUnboundAnalogue:B86Bound:ADPUnbound
3ipyA00UnboundUnboundUnboundUnboundUnbound
3ipyB00UnboundUnboundUnboundUnboundUnbound
3kfxA00UnboundUnboundAnalogue:MCYBound:ADPUnbound
3kfxB00UnboundUnboundAnalogue:MCYBound:ADPUnbound
3mjrA00UnboundUnboundAnalogue:AC2Bound:UDPUnbound
3mjrB00UnboundUnboundAnalogue:AC2Bound:UDPUnbound
3mjrC00UnboundUnboundUnboundBound:UDPUnbound
3mjrD00UnboundUnboundAnalogue:AC2Bound:UDPUnbound
3qejA00UnboundUnboundUnboundBound:UDPUnbound
3qejB00UnboundUnboundUnboundBound:UDPUnbound
3qenA00UnboundUnboundAnalogue:5BTBound:UDPUnbound
3qenB00UnboundUnboundAnalogue:5BTBound:UDPUnbound
3qeoA00UnboundUnboundAnalogue:LLTBound:UDPUnbound
3qeoB00UnboundUnboundAnalogue:LLTBound:UDPUnbound

Active-site residues
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1p5zB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 65-76
1p60A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
 
1p60B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 62-77
1p61B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 65-76
1p62B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 65-76
2a2zA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79
2a2zB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79
2a2zC00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79
2a2zD00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79
2a30A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79, invisible 241-245
2a30B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79, invisible 241-245
2a30C00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79, invisible 241-245
2a30D00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
deletion mutant 65-79, invisible 241-245
2a7qA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 65-76
2no0A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2no0B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 65-76, 117, 243-245
2no1A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 167-168
2no1B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 64-76, 222, 243-245
2no6A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2no6B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-77, 117, 167-168, 244
2no7A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2no7B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 64-77, 115-117, 167-168, 243-245
2no9A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2no9B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-76
2noaA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2noaB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-77, 115-117, 166
2qrnA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qrnB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qrnC00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qrnD00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qroA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qroB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qroC00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2qroD00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 64-76
2zi3A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, E247A
2zi3B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, E247A, invisible 62-79, 117
2zi4A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 64-76
2zi5A00LYS 1034;GLU 1053;ARG 1128;ARG 1192;ARG 1194
SER 1035;GLU 1127(Magnesium binding)
ALA 1032;GLY 1033;LYS 1034
mutant C1009S, C1045S, C1059S, C1146S, invisible 1059-1075, 1114-1118
2zi5B00LYS 2034;GLU 2053;ARG 2128;ARG 2192;ARG 1194
SER 2035;GLU 2127(Magnesium binding)
ALA 2032;GLY 2033;LYS 2034
mutant C2009S, C2045S, C2059S, C2146S, invisible 2061-2072, 2117-2119, 2166-2168
2zi5C00LYS 3034;GLU 3053;ARG 3128;ARG 3192;ARG 3194
SER 3035;GLU 3127(Magnesium binding)
ALA 3032;GLY 3033;LYS 3034
mutant C3009S, C3045S, C3059S, C3146S, invisible 3060-3072, 3114-3119, 3167-3169
2zi5D00LYS 4034;GLU 4053;ARG 4128;ARG 4192;ARG 4194
SER 4035;GLU 4127(Magnesium binding)
ALA 4032;GLY 4033;LYS 4034
mutant C4009S, C4045S, C4059S, C4146S, invisible 4059-4076, 4117-4119, 4168-4169
2zi6A00LYS 1034;GLU 1053;ARG 1128;ARG 1192;ARG 1194
SER 1035;GLU 1127(Magnesium binding)
ALA 1032;GLY 1033;LYS 1034
mutant C1009S, C1045S, C1059S, C1146S, invisible 1059-1077, 1114-1118
2zi6B00LYS 2034;GLU 2053;ARG 2128;ARG 2192;ARG 1194
SER 2035;GLU 2127(Magnesium binding)
ALA 2032;GLY 2033;LYS 2034
mutant C2009S, C2045S, C2059S, C2146S, invisible 2062-2071, 2117-2119, 2166-2168
2zi6C00LYS 3034;GLU 3053;ARG 3128;ARG 3192;ARG 3194
SER 3035;GLU 3127(Magnesium binding)
ALA 3032;GLY 3033;LYS 3034
mutant C3009S, C3045S, C3059S, C3146S, invisible 3060-3075, 3114-3119, 3167-3169
2zi6D00LYS 4034;GLU 4053;ARG 4128;ARG 4192;ARG 4194
SER 4035;GLU 4127(Magnesium binding)
ALA 4032;GLY 4033;LYS 4034
mutant C4009S, C4045S, C4059S, C4146S, invisible 4059-4076, 4117-4119, 4168-4169
2zi7A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 65-77, 222-230
2zi7B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 62-77, 114-120, 221-230
2zi9A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
2zi9B00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-76
2ziaA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 62-77, 114-118
2ziaB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 65-77, 114-115, 224-226
3exkA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant R104M, D133A, invisible 63-77
3hp1A00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant R104M, D133A, invisible 63-77
3ipxA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 65-76
3ipyA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 61-76
3ipyB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
invisible 61-76
3kfxA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 65-76
3kfxB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S
3mjrA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 61-70, 168
3mjrB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 61-74, 167
3mjrC00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 60-73, 167-170
3mjrD00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 59-76, 168
3qejA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 62-69
3qejB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-70
3qenA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 64-69
3qenB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-70
3qeoA00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 62-69
3qeoB00LYS   34;GLU   53;ARG  128;ARG  192;ARG  194
SER   35;GLU  127(Magnesium binding)
ALA   32;GLY   33;LYS   34
mutant C9S, C45S, C59S, C146S, invisible 63-70

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Fig.3, p.514-517
[6]p.137-138
[9]Fig.5

references
[1]
PubMed ID9200705
JournalBiochemistry
Year1997
Volume36
Pages7540-7
AuthorsHughes TL, Hahn TM, Reynolds KK, Shewach DS
TitleKinetic analysis of human deoxycytidine kinase with the true phosphate donor uridine triphosphate.
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PubMed ID10873853
JournalStructure
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Volume8
Pages629-42
AuthorsOstermann N, Schlichting I, Brundiers R, Konrad M, Reinstein J, Veit T, Goody RS, Lavie A
TitleInsights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate.
Related PDB1e2d,1e2e,1e2f,1e2g,1e2q
[3]
PubMed ID11427893
JournalNat Struct Bio
Year2001
Volume8
Pages616-20
AuthorsJohansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B, Eriksson S, Eklund H
TitleStructural basis for substrate specificities of cellular deoxyribonucleoside kinases. Nat Struct Biol.
Related PDB1jag,2ocp
[4]
PubMed ID12363036
JournalCell Mol Life Sci
Year2002
Volume59
Pages1327-46
AuthorsEriksson S, Munch-Petersen B, Johansson K, Eklund H
TitleStructure and function of cellular deoxyribonucleoside kinases
[5]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
PubMed ID12808445
JournalNat Struct Biol
Year2003
Volume10
Pages513-9
AuthorsSabini E, Ort S, Monnerjahn C, Konrad M, Lavie A
TitleStructure of human dCK suggests strategies to improve anticancer and antiviral therapy.
Related PDB1p5z,1p60,1p61,1p62
Related UniProtKBP27707
[6]
PubMed ID16421443
JournalActa Crystallogr D Biol Crystallogr
Year2006
Volume62
Pages133-9
AuthorsZhang Y, Secrist JA 3rd, Ealick SE
TitleThe structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation.
Related PDB2a7q
[7]
PubMed ID16401075
JournalBiochemistry
Year2006
Volume45
Pages452-61
AuthorsGodsey MH, Ort S, Sabini E, Konrad M, Lavie A
TitleStructural basis for the preference of UTP over ATP in human deoxycytidine kinase: illuminating the role of main-chain reorganization.
Related PDB2a2z,2a30
[8]
PubMed ID18084067
JournalActa Crystallogr D Biol Crystallogr
Year2007
Volume63
Pages1201-7
AuthorsSoriano EV, Clark VC, Ealick SE
TitleStructures of human deoxycytidine kinase product complexes.
Related PDB2qrn,2qro
[9]
PubMed ID17530837
JournalJ Med Chem
Year2007
Volume50
Pages3004-14
AuthorsSabini E, Hazra S, Konrad M, Lavie A
TitleNonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides.
Related PDB2no0,2no1,2no6,2no7
[10]
PubMed ID17158155
JournalNucleic Acids Res
Year2007
Volume35
Pages186-92
AuthorsSabini E, Hazra S, Konrad M, Burley SK, Lavie A
TitleStructural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase.
Related PDB2no9,2noa
[11]
PubMed ID18570408
JournalJ Med Chem
Year2008
Volume51
Pages4219-25
AuthorsSabini E, Hazra S, Konrad M, Lavie A
TitleElucidation of different binding modes of purine nucleosides to human deoxycytidine kinase.
Related PDB2zi7,2zi9,2zia
[12]
PubMed ID18377927
JournalJ Mol Biol
Year2008
Volume378
Pages607-21
AuthorsSabini E, Hazra S, Ort S, Konrad M, Lavie A
TitleStructural basis for substrate promiscuity of dCK.
Related PDB2zi3,2zi4,2zi5,2zi6
[13]
PubMed ID19159229
JournalBiochemistry
Year2009
Volume48
Pages1256-63
AuthorsHazra S, Sabini E, Ort S, Konrad M, Lavie A
TitleExtending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase.
Related PDB3exk,3hp1
[14]
PubMed ID19836232
JournalBioorg Med Chem Lett
Year2009
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Pages6784-7
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TitleLead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors.
Related PDB3ipx,3ipy
[15]
PubMed ID20614893
JournalBiochemistry
Year2010
Volume49
Pages6784-90
AuthorsHazra S, Ort S, Konrad M, Lavie A
TitleStructural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues .
Related PDB3kfx
[16]
PubMed ID20684612
JournalJ Med Chem
Year2010
Volume53
Pages5792-800
AuthorsHazra S, Konrad M, Lavie A
TitleThe sugar ring of the nucleoside is required for productive substrate positioning in the active site of human deoxycytidine kinase (dCK): implications for the development of dCK-activated acyclic guanine analogues.
Related PDB3mjr
[17]
PubMed ID21351740
JournalBiochemistry
Year2011
Volume50
Pages2870-80
AuthorsHazra S, Szewczak A, Ort S, Konrad M, Lavie A
TitlePost-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.
Related PDB3qej,3qen,3qeo

comments
This enzyme is a non-enantioselective enzyme, which can phosphorylate both L- and D-enantiomers of nuceloside. Moreover, this enzyme constitute a family of three related non-enantioselective enzymes, along with thymidine kinase (EC 2.7.1.21; UniProt;O00142) and deoxyguanosine kinase (EC 2.7.1.113; UniProt;Q16854). Moreover, this enzyme is also homologous to deoxynucleoside kinase (EC 2.7.1.145; S00672 in EzCatDB).
This enzyme catalyzes transfer of phosphoryl group from NTP to 5'-hydroxyl group of deoxycytidine, as follows:
(0) Arg128 may modulate the activity of Glu53. Magnesium ion, bound to Ser35 and Glu127, may stabilize the negative charge on the beta- and gamma-phosphate groups.
(1) Glu53 acts as a general base to deprotonate and activate 5'-hydroxyl group of the substrate, deoxycytidine.
(2) The activated 5'-hydroxyl oxygen makes a nucleophilic attack on the gamma-phosphate group of NTP. (SN2-like reaction)
(3) During the transition state, Arg128, Arg192 and Arg194 may stabilize the transferrd group, the gamma-phosphate, whereas the sidechain of Lys34 and Arg192 might stabilize the leaving group, beta- and alpha-phosphate groups, along with the mainchain of Ala32, Gly33, and Lys34. At the same time, the magnesium ion might stabilize the negative charge on the transferred group, the gamma-phosphate, and the leaving group, the beta-phosphate group.

createdupdated
2009-10-202012-02-29


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)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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