EzCatDB: S00303
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DB codeS00303
RLCP classification3.103.70800.502 : Transfer
CATH domainDomain 13.40.50.300 : Rossmann foldCatalytic domain
E.C.2.7.1.25

CATH domainRelated DB codes (homologues)
3.40.50.300 : Rossmann foldS00527,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

Enzyme Name
UniProtKBKEGG

Q12657
Protein nameAdenylyl-sulfate kinaseadenylyl-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
SynonymsEC 2.7.1.25
Adenosine-5''-phosphosulfate kinase
APS kinase
ATP adenosine-5''-phosphosulfate 3''-phosphotransferase
PfamPF01583 (APS_kinase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism
MAP00450Selenoamino acid metabolism
MAP00920Sulfur metabolism

UniProtKB:Accession NumberQ12657
Entry nameKAPS_PENCH
ActivityATP + adenylyl sulfate = ADP + 3''- phosphoadenylyl sulfate.
SubunitHomodimer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00224C00008C00053
CompoundmagnesiumATPAdenylylsulfateADP3'-Phosphoadenylylsulfate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamine group,nucleotide,sulfate groupamine group,nucleotideamine group,nucleotide,sulfate group
ChEBI18420
15422
17709
16761
17980
PubChem888
5957
10238
6022
10214
             
1d6jAUnboundUnboundUnboundUnboundUnbound
1d6jBUnboundUnboundUnboundUnboundUnbound
1m7gAUnboundUnboundBound:ADXAnalogue:AV2Unbound
1m7gBUnboundUnboundBound:ADXBound:ADPUnbound
1m7gCUnboundUnboundBound:ADXAnalogue:AV2Unbound
1m7gDUnboundUnboundBound:ADXBound:ADPUnbound
1m7hAUnboundUnboundUnboundBound:ADPUnbound
1m7hBUnboundUnboundBound:ADXBound:ADPUnbound
1m7hCUnboundUnboundUnboundBound:ADPUnbound
1m7hDUnboundUnboundBound:ADXBound:ADPUnbound

Active-site residues
resource
literature [8](Mg2+ binding), [9](phosphoryl transfer), [10]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1d6jASER 34;LYS 38;       ;       
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
invisible 144-169
1d6jBSER 34;LYS 38;       ;       
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
invisible 144-169
1m7gASER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7gBSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7gCSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7gDSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7hASER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7hBSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7hCSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 
1m7hDSER 34;LYS 38;LYS 151;TYR 154
SER 39;ASP 61(Mg2+ binding)
ALA 35;SER 36;GLY 37
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.13678-13679

references
[1]
PubMed ID2542310
JournalJ Biol Chem
Year1989
Volume264
Pages9433-7
AuthorsRenosto F, Martin RL, Segel IH
TitleSulfate-activating enzymes of Penicillium chrysogenum. The ATP sulfurylase.adenosine 5'-phosphosulfate complex does not serve as a substrate for adenosine 5'-phosphosulfate kinase.
[2]
PubMed ID1846515
JournalArch Biochem Biophys
Year1991
Volume284
Pages30-4
AuthorsRenosto F, Martin RL, Segel IH
TitleAdenosine-5'-phosphosulfate kinase from Penicillium chrysogenum: ligand binding properties and the mechanism of substrate inhibition.
[3]
PubMed ID8204616
JournalBiochemistry
Year1994
Volume33
Pages6822-7
AuthorsLyle S, Ozeran JD, Stanczak J, Westley J, Schwartz NB
TitleIntermediate channeling between ATP sulfurylase and adenosine 5'-phosphosulfate kinase from rat chondrosarcoma.
[4]
PubMed ID9786849
JournalJ Biol Chem
Year1998
Volume273
Pages28583-9
AuthorsMacRae IJ, Rose AB, Segel IH
TitleAdenosine 5'-phosphosulfate kinase from Penicillium chrysogenum. site-directed mutagenesis at putative phosphoryl-accepting and ATP P-loop residues.
[5]
PubMed ID9882457
JournalArch Biochem Biophys
Year1999
Volume361
Pages277-82
AuthorsMacRae IJ, Segel IH
TitleAdenosine 5'-phosphosulfate (APS) kinase: diagnosing the mechanism of substrate inhibition.
[6]
PubMed ID10196147
JournalJ Biol Chem
Year1999
Volume274
Pages10751-7
AuthorsDeyrup AT, Krishnan S, Singh B, Schwartz NB
TitleActivity and stability of recombinant bifunctional rearranged and monofunctional domains of ATP-sulfurylase and adenosine 5'-phosphosulfate kinase.
[7]
PubMed ID10956658
JournalJ Biol Chem
Year2000
Volume275
Pages36303-10
AuthorsMacRae IJ, Hanna E, Ho JD, Fisher AJ, Segel IH
TitleInduction of positive cooperativity by amino acid replacements within the C-terminal domain of Penicillium chrysogenum ATP sulfurylase.
[8]
PubMed ID10677210
JournalBiochemistry
Year2000
Volume39
Pages1613-21
AuthorsMacRae IJ, Segel IH, Fisher AJ
TitleCrystal structure of adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
Related PDB1d6j
[9]
PubMed ID12427029
JournalBiochemistry
Year2002
Volume41
Pages13672-80
AuthorsLansdon EB, Segel IH, Fisher AJ
TitleLigand-induced structural changes in adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
Related PDB1m7g,1m7h
[10]
PubMed ID15755455
JournalJ Mol Biol
Year2005
Volume347
Pages623-35
AuthorsHarjes S, Bayer P, Scheidig AJ
TitleThe crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding.
Related PDB1x6v,1xjq,1xnj

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.

createdupdated
2002-05-202009-02-26


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