DB code: S00303

RLCP classification 3.103.70800.502 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.7.1.25
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 S00682 S00913 S00914 S00301 S00302 S00304 S00307 S00308 S00305 S00306 S00309 S00310 S00311 M00114 M00199 D00129 D00130 D00540 M00186

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q12657 Adenylyl-sulfate kinase
EC 2.7.1.25
Adenosine-5''-phosphosulfate kinase
APS kinase
ATP adenosine-5''-phosphosulfate 3''-phosphotransferase
PF01583 (APS_kinase)
[Graphical View]

KEGG enzyme name
adenylyl-sulfate kinase
adenylylsulfate kinase (phosphorylating)
5'-phosphoadenosine sulfate kinase
adenosine 5'-phosphosulfate kinase
adenosine phosphosulfate kinase
adenosine phosphosulfokinase
adenosine-5'-phosphosulfate-3'-phosphokinase
APS kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q12657 KAPS_PENCH ATP + adenylyl sulfate = ADP + 3''- phosphoadenylyl sulfate. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism
MAP00450 Selenoamino acid metabolism
MAP00920 Sulfur metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00224 C00008 C00053
E.C.
Compound magnesium ATP Adenylylsulfate ADP 3'-Phosphoadenylylsulfate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amine group,nucleotide ,sulfate group amine group,nucleotide amine group,nucleotide ,sulfate group
ChEBI 18420
15422
17709
16761
17980
PubChem 888
5957
10238
6022
10214
1d6jA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1d6jB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1m7gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Analogue:AV2 Unbound
1m7gB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Bound:ADP Unbound
1m7gC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Analogue:AV2 Unbound
1m7gD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Bound:ADP Unbound
1m7hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:ADP Unbound
1m7hB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Bound:ADP Unbound
1m7hC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:ADP Unbound
1m7hD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADX Bound:ADP Unbound

Reference for Active-site residues
resource references E.C.
literature [8](Mg2+ binding), [9](phosphoryl transfer), [10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d6jA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38; ; SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37 invisible 144-169
1d6jB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38; ; SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37 invisible 144-169
1m7gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7gB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7gC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7gD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7hB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7hC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37
1m7hD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 34;LYS 38;LYS 151;TYR 154 SER 39;ASP 61(Mg2+ binding) ALA 35;SER 36;GLY 37

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.13678-13679

References
[1]
Resource
Comments
Medline ID
PubMed ID 2542310
Journal J Biol Chem
Year 1989
Volume 264
Pages 9433-7
Authors Renosto F, Martin RL, Segel IH
Title Sulfate-activating enzymes of Penicillium chrysogenum. The ATP sulfurylase.adenosine 5'-phosphosulfate complex does not serve as a substrate for adenosine 5'-phosphosulfate kinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1846515
Journal Arch Biochem Biophys
Year 1991
Volume 284
Pages 30-4
Authors Renosto F, Martin RL, Segel IH
Title Adenosine-5'-phosphosulfate kinase from Penicillium chrysogenum: ligand binding properties and the mechanism of substrate inhibition.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8204616
Journal Biochemistry
Year 1994
Volume 33
Pages 6822-7
Authors Lyle S, Ozeran JD, Stanczak J, Westley J, Schwartz NB
Title Intermediate channeling between ATP sulfurylase and adenosine 5'-phosphosulfate kinase from rat chondrosarcoma.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9786849
Journal J Biol Chem
Year 1998
Volume 273
Pages 28583-9
Authors MacRae IJ, Rose AB, Segel IH
Title Adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum. site-directed mutagenesis at putative phosphoryl-accepting and ATP P-loop residues.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9882457
Journal Arch Biochem Biophys
Year 1999
Volume 361
Pages 277-82
Authors MacRae IJ, Segel IH
Title Adenosine 5'-phosphosulfate (APS) kinase: diagnosing the mechanism of substrate inhibition.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10196147
Journal J Biol Chem
Year 1999
Volume 274
Pages 10751-7
Authors Deyrup AT, Krishnan S, Singh B, Schwartz NB
Title Activity and stability of recombinant bifunctional rearranged and monofunctional domains of ATP-sulfurylase and adenosine 5'-phosphosulfate kinase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10956658
Journal J Biol Chem
Year 2000
Volume 275
Pages 36303-10
Authors MacRae IJ, Hanna E, Ho JD, Fisher AJ, Segel IH
Title Induction of positive cooperativity by amino acid replacements within the C-terminal domain of Penicillium chrysogenum ATP sulfurylase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10677210
Journal Biochemistry
Year 2000
Volume 39
Pages 1613-21
Authors MacRae IJ, Segel IH, Fisher AJ
Title Crystal structure of adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
Related PDB 1d6j
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 12427029
Journal Biochemistry
Year 2002
Volume 41
Pages 13672-80
Authors Lansdon EB, Segel IH, Fisher AJ
Title Ligand-induced structural changes in adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
Related PDB 1m7g 1m7h
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 15755455
Journal J Mol Biol
Year 2005
Volume 347
Pages 623-35
Authors Harjes S, Bayer P, Scheidig AJ
Title The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding.
Related PDB 1x6v 1xjq 1xnj
Related UniProtKB

Comments
According to the literature [9], Ser34 might serve as the phosphoryl acceptor, which forms a phosphorylated enzyme intermediate. Although the paper [8] suggests that Asp61 might bind to Mg2+ ion, the paper [9] mentioned that it is still unknown if Asp61 acts as a Walker B motif by coordinating a water which is coordinated to Mg2+. Possibly, the gamma-phosphate of ATP or an analogue is needed in order for Mg2+ to bind to the APS kinase [9].
Considering the active site structure with ligand molecules, the reaction should proceed via single-displacement mehcanism, as observed in the other homologous enzymes, suggesting that Ser34 should not be a nucleophile. Moreover, Tyr154, which is conserved also in the human orthologous enzyme (PDB;1xnj), might activate the acceptor group, 3'-OH of APS substrate, through the sidechain of Ser34. Taken together, the reaction proceeds as follows:
(1) Tyr154 act as a general base to activate the 3'-hydroxyl of substrate, APS, through the sidechain of Ser34.
(2) The activated hydroxyl oxygen makes a nucleophilic attack on the transferred group, the gamma-phosphate, of ATP.
(3) The transition-state must be stabilized by sidechains of Lys38 and Lys151, and mainchain amide groups of Ala35-Gly37, along with a magnesium ion, which should be bound to Ser39 and Asp61. (The magnesium must be bound to the transferred phosphate.)
(4) Finally, the transferred phosphate is moved to the 3'-hydroxyl oxygen, with release of ADP.

Created Updated
2002-05-20 2009-02-26