DB code: S00682

RLCP classification 3.103.69910.364 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.7.1.74
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.300 : Rossmann fold S00527 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P27707 Deoxycytidine kinase
dCK
EC 2.7.1.74
NP_000779.1 (Protein)
NM_000788.2 (DNA/RNA sequence)
PF01712 (dNK)
[Graphical View]

KEGG enzyme name
Deoxycytidine kinase
Deoxycytidine kinase (phosphorylating)
2'-Deoxycytidine kinase
Ara-C kinase
Arabinofuranosylcytosine kinase
Deoxycytidine-cytidine kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P27707 DCK_HUMAN NTP + deoxycytidine = NDP + dCMP. Homodimer. Nucleus.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism
MAP00240 Pyrimidine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00201 C00881 C00454 C00239
E.C.
Compound Magnesium NTP deoxycytidine NDP dCMP
Type divalent metal (Ca2+, Mg2+) nucleotide amine group,nucleoside nucleotide amine group,nucleotide
ChEBI 18420
 18420
 		15698
 15698
 		15918
 15918
PubChem 888
 888
 		13711
 13711
 		13945
 13945
1p5zB00 Bound:_MG Unbound Analogue:AR3 Bound:ADP Unbound
1p60A00 Unbound Unbound Bound:DCZ Bound:ADP Unbound
1p60B00 Unbound Unbound Bound:DCZ Bound:ADP Unbound
1p61B00 Unbound Unbound Bound:DCZ Bound:ADP Unbound
1p62B00 Bound:_MG Unbound Analogue:GEO Bound:ADP Unbound
2a2zA00 Bound:_MG Unbound Bound:DCZ Bound:UDP Unbound
2a2zB00 Bound:_MG Unbound Bound:DCZ Bound:UDP Unbound
2a2zC00 Bound:_MG Unbound Bound:DCZ Bound:UDP Unbound
2a2zD00 Bound:_MG Unbound Bound:DCZ Bound:UDP Unbound
2a30A00 Unbound Unbound Bound:DCZ Unbound Unbound
2a30B00 Unbound Unbound Bound:DCZ Unbound Unbound
2a30C00 Unbound Unbound Bound:DCZ Unbound Unbound
2a30D00 Unbound Unbound Bound:DCZ Unbound Unbound
2a7qA00 Bound:_MG Unbound Analogue:CFB Bound:ADP Unbound
2no0A00 Unbound Unbound Analogue:GEO Bound:ADP Unbound
2no0B00 Unbound Unbound Analogue:GEO Bound:ADP Unbound
2no1A00 Unbound Unbound Bound:DCZ Bound:ADP Unbound
2no1B00 Unbound Unbound Bound:DCZ Bound:ADP Unbound
2no6A00 Unbound Unbound Analogue:ETV Bound:ADP Unbound
2no6B00 Unbound Unbound Analogue:ETV Bound:ADP Unbound
2no7A00 Unbound Unbound Analogue:LDC Bound:ADP Unbound
2no7B00 Unbound Unbound Analogue:LDC Bound:ADP Unbound
2no9A00 Unbound Unbound Analogue:LTT Bound:ADP Unbound
2no9B00 Unbound Unbound Analogue:LTT Bound:ADP Unbound
2noaA00 Unbound Unbound Analogue:3TC Bound:ADP Unbound
2noaB00 Unbound Unbound Analogue:3TC Bound:ADP Unbound
2qrnA00 Bound:_MG Unbound Unbound Bound:UDP Bound:DCM
2qrnB00 Bound:_MG Unbound Unbound Bound:UDP Bound:DCM
2qrnC00 Bound:_MG Unbound Unbound Bound:UDP Bound:DCM
2qrnD00 Bound:_MG Unbound Unbound Bound:UDP Bound:DCM
2qroA00 Bound:_MG Unbound Unbound Bound:UDP Analogue:D5M
2qroB00 Bound:_MG Unbound Unbound Bound:UDP Analogue:D5M
2qroC00 Bound:_MG Unbound Unbound Bound:UDP Analogue:D5M
2qroD00 Bound:_MG Unbound Unbound Bound:UDP Analogue:D5M
2zi3A00 Unbound Unbound Analogue:3D1 Bound:ADP Unbound
2zi3B00 Unbound Unbound Analogue:3D1 Bound:ADP Unbound
2zi4A00 Bound:_MG Unbound Analogue:3L1 Bound:ADP Unbound
2zi5A00 Unbound Unbound Analogue:3L1 Bound:UDP Unbound
2zi5B00 Unbound Unbound Analogue:3L1 Bound:UDP Unbound
2zi5C00 Unbound Unbound Analogue:3L1 Bound:UDP Unbound
2zi5D00 Unbound Unbound Analogue:3L1 Bound:UDP Unbound
2zi6A00 Unbound Unbound Analogue:3D1 Bound:UDP Unbound
2zi6B00 Unbound Unbound Analogue:3D1 Bound:UDP Unbound
2zi6C00 Unbound Unbound Analogue:3D1 Bound:UDP Unbound
2zi6D00 Unbound Unbound Analogue:3D1 Bound:UDP Unbound
2zi7A00 Unbound Unbound Analogue:GNG Bound:UDP Unbound
2zi7B00 Unbound Unbound Analogue:GNG Bound:UDP Unbound
2zi9A00 Unbound Unbound Analogue:CL9 Bound:ADP Unbound
2zi9B00 Unbound Unbound Analogue:CL9 Bound:ADP Unbound
2ziaA00 Unbound Unbound Analogue:CL9 Bound:UDP Unbound
2ziaB00 Unbound Unbound Analogue:CL9 Bound:UDP Unbound
3exkA00 Unbound Unbound Analogue:THM Bound:ADP Unbound
3hp1A00 Unbound Unbound Analogue:LLT Bound:ADP Unbound
3ipxA00 Bound:_MG Unbound Analogue:B86 Bound:ADP Unbound
3ipyA00 Unbound Unbound Unbound Unbound Unbound
3ipyB00 Unbound Unbound Unbound Unbound Unbound
3kfxA00 Unbound Unbound Analogue:MCY Bound:ADP Unbound
3kfxB00 Unbound Unbound Analogue:MCY Bound:ADP Unbound
3mjrA00 Unbound Unbound Analogue:AC2 Bound:UDP Unbound
3mjrB00 Unbound Unbound Analogue:AC2 Bound:UDP Unbound
3mjrC00 Unbound Unbound Unbound Bound:UDP Unbound
3mjrD00 Unbound Unbound Analogue:AC2 Bound:UDP Unbound
3qejA00 Unbound Unbound Unbound Bound:UDP Unbound
3qejB00 Unbound Unbound Unbound Bound:UDP Unbound
3qenA00 Unbound Unbound Analogue:5BT Bound:UDP Unbound
3qenB00 Unbound Unbound Analogue:5BT Bound:UDP Unbound
3qeoA00 Unbound Unbound Analogue:LLT Bound:UDP Unbound
3qeoB00 Unbound Unbound Analogue:LLT Bound:UDP Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1p5zB00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 65-76
1p60A00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34
1p60B00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 62-77
1p61B00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 65-76
1p62B00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 65-76
2a2zA00 LYS 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
2a2zB00 LYS 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
2a2zC00 LYS 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
2a2zD00 LYS 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
2a30A00 LYS 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
2a30B00 LYS 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
2a30C00 LYS 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
2a30D00 LYS 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
2a7qA00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 65-76
2no0A00 LYS 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
2no0B00 LYS 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
2no1A00 LYS 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
2no1B00 LYS 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
2no6A00 LYS 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
2no6B00 LYS 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
2no7A00 LYS 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
2no7B00 LYS 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
2no9A00 LYS 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
2no9B00 LYS 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
2noaA00 LYS 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
2noaB00 LYS 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
2qrnA00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qrnB00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qrnC00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qrnD00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qroA00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qroB00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qroC00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2qroD00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 64-76
2zi3A00 LYS 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
2zi3B00 LYS 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
2zi4A00 LYS 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
2zi5A00 LYS 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
2zi5B00 LYS 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
2zi5C00 LYS 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
2zi5D00 LYS 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
2zi6A00 LYS 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
2zi6B00 LYS 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
2zi6C00 LYS 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
2zi6D00 LYS 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
2zi7A00 LYS 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
2zi7B00 LYS 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
2zi9A00 LYS 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
2zi9B00 LYS 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
2ziaA00 LYS 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
2ziaB00 LYS 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
3exkA00 LYS 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
3hp1A00 LYS 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
3ipxA00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 65-76
3ipyA00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 61-76
3ipyB00 LYS 34;GLU 53;ARG 128;ARG 192;ARG 194 SER 35;GLU 127(Magnesium binding) ALA 32;GLY 33;LYS 34 invisible 61-76
3kfxA00 LYS 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
3kfxB00 LYS 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
3mjrA00 LYS 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
3mjrB00 LYS 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
3mjrC00 LYS 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
3mjrD00 LYS 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
3qejA00 LYS 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
3qejB00 LYS 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
3qenA00 LYS 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
3qenB00 LYS 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
3qeoA00 LYS 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
3qeoB00 LYS 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
References Sections No. of steps in catalysis
[5]
Fig.3, p.514-517
[6]
p.137-138
[9]
Fig.5

References
[1]
Resource
Comments
Medline ID
PubMed ID 9200705
Journal Biochemistry
Year 1997
Volume 36
Pages 7540-7
Authors Hughes TL, Hahn TM, Reynolds KK, Shewach DS
Title Kinetic analysis of human deoxycytidine kinase with the true phosphate donor uridine triphosphate.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10873853
Journal Structure
Year 2000
Volume 8
Pages 629-42
Authors Ostermann N, Schlichting I, Brundiers R, Konrad M, Reinstein J, Veit T, Goody RS, Lavie A
Title Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate.
Related PDB 1e2d 1e2e 1e2f 1e2g 1e2q
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 11427893
Journal Nat Struct Bio
Year 2001
Volume 8
Pages 616-20
Authors Johansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B, Eriksson S, Eklund H
Title Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Nat Struct Biol.
Related PDB 1jag 2ocp
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12363036
Journal Cell Mol Life Sci
Year 2002
Volume 59
Pages 1327-46
Authors Eriksson S, Munch-Petersen B, Johansson K, Eklund H
Title Structure and function of cellular deoxyribonucleoside kinases
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID
PubMed ID 12808445
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 513-9
Authors Sabini E, Ort S, Monnerjahn C, Konrad M, Lavie A
Title Structure of human dCK suggests strategies to improve anticancer and antiviral therapy.
Related PDB 1p5z 1p60 1p61 1p62
Related UniProtKB P27707
[6]
Resource
Comments
Medline ID
PubMed ID 16421443
Journal Acta Crystallogr D Biol Crystallogr
Year 2006
Volume 62
Pages 133-9
Authors Zhang Y, Secrist JA 3rd, Ealick SE
Title The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation.
Related PDB 2a7q
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16401075
Journal Biochemistry
Year 2006
Volume 45
Pages 452-61
Authors Godsey MH, Ort S, Sabini E, Konrad M, Lavie A
Title Structural basis for the preference of UTP over ATP in human deoxycytidine kinase: illuminating the role of main-chain reorganization.
Related PDB 2a2z 2a30
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 18084067
Journal Acta Crystallogr D Biol Crystallogr
Year 2007
Volume 63
Pages 1201-7
Authors Soriano EV, Clark VC, Ealick SE
Title Structures of human deoxycytidine kinase product complexes.
Related PDB 2qrn 2qro
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 17530837
Journal J Med Chem
Year 2007
Volume 50
Pages 3004-14
Authors Sabini E, Hazra S, Konrad M, Lavie A
Title Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides.
Related PDB 2no0 2no1 2no6 2no7
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 17158155
Journal Nucleic Acids Res
Year 2007
Volume 35
Pages 186-92
Authors Sabini E, Hazra S, Konrad M, Burley SK, Lavie A
Title Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase.
Related PDB 2no9 2noa
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 18570408
Journal J Med Chem
Year 2008
Volume 51
Pages 4219-25
Authors Sabini E, Hazra S, Konrad M, Lavie A
Title Elucidation of different binding modes of purine nucleosides to human deoxycytidine kinase.
Related PDB 2zi7 2zi9 2zia
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 18377927
Journal J Mol Biol
Year 2008
Volume 378
Pages 607-21
Authors Sabini E, Hazra S, Ort S, Konrad M, Lavie A
Title Structural basis for substrate promiscuity of dCK.
Related PDB 2zi3 2zi4 2zi5 2zi6
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 19159229
Journal Biochemistry
Year 2009
Volume 48
Pages 1256-63
Authors Hazra S, Sabini E, Ort S, Konrad M, Lavie A
Title Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase.
Related PDB 3exk 3hp1
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 19836232
Journal Bioorg Med Chem Lett
Year 2009
Volume 19
Pages 6784-7
Authors Jessop TC, Tarver JE, Carlsen M, Xu A, Healy JP, Heim-Riether A, Fu Q, Taylor JA, Augeri DJ, Shen M, Stouch TR, Swanson RV, Tari LW, Hunter M, Hoffman I, Keyes PE, Yu XC, Miranda M, Liu Q, Swaffield JC, David Kimball S, Nouraldeen A, Wilson AG, Foushee AM, Jhaver K, Finch R, Anderson S, Oravecz T, Carson KG
Title Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors.
Related PDB 3ipx 3ipy
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 20614893
Journal Biochemistry
Year 2010
Volume 49
Pages 6784-90
Authors Hazra S, Ort S, Konrad M, Lavie A
Title Structural and kinetic characterization of human deoxycytidine kinase variants able to phosphorylate 5-substituted deoxycytidine and thymidine analogues .
Related PDB 3kfx
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 20684612
Journal J Med Chem
Year 2010
Volume 53
Pages 5792-800
Authors Hazra S, Konrad M, Lavie A
Title The 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 PDB 3mjr
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 21351740
Journal Biochemistry
Year 2011
Volume 50
Pages 2870-80
Authors Hazra S, Szewczak A, Ort S, Konrad M, Lavie A
Title Post-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 PDB 3qej 3qen 3qeo
Related UniProtKB

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.

Created Updated
2009-10-20 2012-02-29