EzCatDB: S00678
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DB codeS00678
RLCP classification3.103.70035.456 : Transfer
CATH domainDomain 13.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineCatalytic domain
E.C.2.7.1.35

CATH domainRelated DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineS00534,S00541,S00705,S00903,S00904,S00905,S00453,D00416

Enzyme Name
UniProtKBKEGG

P82197O00764
Protein namePyridoxal kinasePyridoxal kinasePyridoxal kinase
Pyridoxal kinase (phosphorylating)
Pyridoxal 5-phosphate-kinase
Pyridoxal phosphokinase
Pyridoxine kinase
SynonymsEC 2.7.1.35
Pyridoxine kinase
EC 2.7.1.35
Pyridoxine kinase
RefSeqNP_001009220.1 (Protein)
NM_001009220.1 (DNA/RNA sequence)
NP_003672.1 (Protein)
NM_003681.4 (DNA/RNA sequence)
PfamPF00294 (PfkB)
[Graphical view]
PF00294 (PfkB)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00750Vitamin B6 metabolism

UniProtKB:Accession NumberP82197O00764
Entry namePDXK_SHEEPPDXK_HUMAN
ActivityATP + pyridoxal = ADP + pyridoxal 5'-phosphate.ATP + pyridoxal = ADP + pyridoxal 5'-phosphate.
SubunitHomodimer.Homodimer (Probable).
Subcellular locationCytoplasm.Cytoplasm.
CofactorDivalent cations. Zn(2+) is more efficient than Mg(2+).Divalent cations. Zn(2+) is more efficient than Mg(2+).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00038C00238C00002C00250C00008C00018
CompoundMagnesiumZincPotassiumATPpyridoxalADPpyridoxal 5'-phosphate
Typedivalent metal (Ca2+, Mg2+)heavy metalunivalent metal (Na+, K+)amine group,nucleotidearomatic ring (with nitrogen atoms),carbohydrateamine group,nucleotidearomatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI18420
29105
29103
15422
17310
16761
18405
PubChem888
32051
813
5957
1050
6022
1051
               
1lhpA00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1lhpB00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1lhrA00UnboundBound:_ZNBound:__KBound:ATPUnboundUnboundUnbound
1lhrB00UnboundBound:_ZNBound:__KBound:ATPUnboundUnboundUnbound
1rftA00UnboundBound:_ZNBound:__KAnalogue:ACPAnalogue:PXMUnboundUnbound
1rfuA00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuB00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuC00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuD00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuE00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuF00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuG00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfuH00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPBound:PLP
1rfvA00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPUnbound
1rfvB00UnboundBound:_ZNUnboundUnboundUnboundBound:ADPUnbound
1ygjA00UnboundUnboundUnboundUnboundAnalogue:RMCUnboundUnbound
1ygkA00UnboundUnboundUnboundUnboundAnalogue:RRCUnboundUnbound
1yhjA00UnboundUnboundUnboundUnboundAnalogue:R6CUnboundUnbound
2ajpA00Bound:_MGUnboundUnboundAnalogue:ANPUnboundUnboundUnbound
2ajpB00Bound:_MGUnboundUnboundAnalogue:ANPUnboundUnboundUnbound
2f7kA00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
2f7kB00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
2yxtA00UnboundUnboundAnalogue:_NAUnboundUnboundUnboundUnbound
2yxtB00UnboundUnboundAnalogue:_NAUnboundUnboundUnboundUnbound
2yxuA00Bound:_MGUnboundAnalogue:_NABound:ATPUnboundUnboundUnbound
2yxuB00Bound:_MGUnboundAnalogue:_NABound:ATPUnboundUnboundUnbound
3fhxA00Bound:_MGUnboundAnalogue:_NABound:ATPBound:PXLUnboundUnbound
3fhxB00Bound:_MGUnboundAnalogue:_NABound:ATPBound:PXLUnboundBound:PLP
3fhyA00Bound:_MGUnboundAnalogue:_NABound:ATPUnboundUnboundUnbound
3fhyB00Bound:_MGUnboundAnalogue:_NABound:ATPUnboundUnboundUnbound

Active-site residues
resource
literature [6], [8], [11], [14], [15]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1lhpA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1lhpB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1lhrA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1lhrB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rftA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuC00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuD00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuE00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuF00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuG00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfuH00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfvA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1rfvB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1ygjA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1ygkA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
1yhjA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2ajpA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2ajpB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2f7kA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2f7kB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2yxtA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2yxtB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2yxuA00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
2yxuB00ASP 235
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;ASP 235
 
3fhxA00       
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;       
mutant D235A
3fhxB00       
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;       
mutant D235A
3fhyA00       
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;       
mutant D235N
3fhyB00       
ASP 113;GLU 153(pottasium binding);ASP 118(magnesium binding);THR 148;THR 186(monovalent cation binding)
GLY 232;THR 233;GLY 234;       
mutant D235N

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Fig.5, p.46387-46389
[8]p.17462, p.17464-17465
[11]p.1305
[14]p.2191
[15]Scheme 1, p.14

references
[1]
PubMed ID16590515
JournalProc Natl Acad Sci U S A
Year1959
Volume45
Pages1371-9
AuthorsMcCormick DB, Snell EE
TitlePYRIDOXAL KINASE OF HUMAN BRAIN AND ITS INHIBITION BY HYDRAZINE DERIVATIVES.
[2]
PubMed ID6288708
JournalJ Biol Chem
Year1982
Volume257
Pages12136-40
AuthorsChurchich JE, Wu C
TitleNucleoside phosphorothioates as probes of the nucleotide binding site of brain pyridoxal kinase.
[3]
PubMed ID9252787
JournalEnzyme Protein
Year1996
Volume49
Pages291-304
AuthorsLaine-Cessac P, Allain P
TitleKinetic studies of the effects of K+, Na+ and Li+ on the catalytic activity of human erythrocyte pyridoxal kinase.
[4]
PubMed ID9843365
JournalBiochemistry
Year1998
Volume37
Pages15607-20
AuthorsMathews II, Erion MD, Ealick SE
TitleStructure of human adenosine kinase at 1.5 A resolution.
[5]
PubMed ID9519409
JournalStructure
Year1998
Volume6
Pages183-93
AuthorsSigrell JA, Cameron AD, Jones TA, Mowbray SL
TitleStructure of Escherichia coli ribokinase in complex with ribose and dinucleotide determined to 1.8 A resolution: insights into a new family of kinase structures.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH SUBSTRATE; ADP AND COFACTOR.
PubMed ID12235162
JournalJ Biol Chem
Year2002
Volume277
Pages46385-90
AuthorsLi MH, Kwok F, Chang WR, Lau CK, Zhang JP, Lo SC, Jiang T, Liang DC
TitleCrystal structure of brain pyridoxal kinase, a novel member of the ribokinase superfamily.
Related PDB1lhp,1lhr
Related UniProtKBP82197
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 2-287, SUBUNIT.
PubMed ID15547280
JournalJ Bacteriol
Year2004
Volume186
Pages8074-82
AuthorsSafo MK, Musayev FN, Hunt S, di Salvo ML, Scarsdale N, Schirch V
TitleCrystal structure of the PdxY Protein from Escherichia coli.
Related PDB1td2
Related UniProtKBP77150
[8]
PubMed ID14722069
JournalJ Biol Chem
Year2004
Volume279
Pages17459-65
AuthorsLi MH, Kwok F, Chang WR, Liu SQ, Lo SC, Zhang JP, Jiang T, Liang DC
TitleConformational changes in the reaction of pyridoxal kinase.
Related PDB1rft,1rfu,1rfv
[9]
PubMed ID15985434
JournalJ Biol Chem
Year2005
Volume280
Pages31220-9
AuthorsTang L, Li MH, Cao P, Wang F, Chang WR, Bach S, Reinhardt J, Ferandin Y, Galons H, Wan Y, Gray N, Meijer L, Jiang T, Liang DC
TitleCrystal structure of pyridoxal kinase in complex with roscovitine and derivatives.
Related PDB1ygk,1ygj,1yhj
[10]
PubMed ID16740960
JournalJ Bacteriol
Year2006
Volume188
Pages4542-52
AuthorsSafo MK, Musayev FN, di Salvo ML, Hunt S, Claude JB, Schirch V
TitleCrystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases.
Related PDB2ddm,2ddo,2ddw
[11]
PubMed ID16267046
JournalJ Biol Chem
Year2006
Volume281
Pages1305-8
AuthorsDi Cera E
TitleA structural perspective on enzymes activated by monovalent cations.
[12]
PubMed ID16600635
JournalJ Struct Biol
Year2006
Volume154
Pages327-32
AuthorsCao P, Gong Y, Tang L, Leung YC, Jiang T
TitleCrystal structure of human pyridoxal kinase.
Related PDB2f7k
[13]
PubMed ID17015484
JournalPhysiol Rev
Year2006
Volume86
Pages1049-92
AuthorsPage MJ, Di Cera E
TitleRole of Na+ and K+ in enzyme function.
[14]
PubMed ID17766369
JournalProtein Sci
Year2007
Volume16
Pages2184-94
AuthorsMusayev FN, di Salvo ML, Ko TP, Gandhi AK, Goswami A, Schirch V, Safo MK
TitleCrystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation.
Related PDB2yxt,2yxu
[15]
PubMed ID19351586
JournalBiochem Biophys Res Commun
Year2009
Volume381
Pages12-5
AuthorsGandhi AK, Ghatge MS, Musayev FN, Sease A, Aboagye SO, di Salvo ML, Schirch V, Safo MK
TitleKinetic and structural studies of the role of the active site residue Asp235 of human pyridoxal kinase.
Related PDB3fhx,3fhy

comments
This enzyme belongs to ribokinase superfamily (see [12] and [13]).
This enzyme, pyridoxal kinase (EC 2.7.1.35), can be classified into three groups, based on the sequence and the metal binding sites (see [10]).
This enzyme belongs to Eukaryote pdxK group, whereas the counterpart enzymes from prokaryote can be classified into two groups, Prokaryote pdxK group (S00903 in EzCatDB) and Prokaryote pdxY group (S00904 in EzCatDB) (see [10]).
This enzyme belongs to the K+ activated type I enzymes (see [11] & [13]).
For this enzyme, zinc ion is more efficiant cofactor than magnesium ion. Whereas zinc ion is bound to beta- and gamma-phosphate groups of ATP, magnesium ion is bound to alpha- and beta-phosphate groups as well as Asp118. Thus, these divalent metal ions interacts with the enzyme and substrate differently from each other.
Meanwhile, potassium and sodium ions are bound to more similar position. However, whereas potassium ion is bound to Asp113, Glu153, Thr148 and Thr186 as well as beta-phosphate of ATP, sodium ion is bound to Thr148 and Thr186 as well as ATP gamma-phosphate.
According to the literature [8] and [14], the reaction preceeds as follows:
(0) Zinc ion stabilizes the negatively-charged transferred group (gamma-phosphate) and leaving group (beta-phosphate) of ATP, whereas potassium ion, bound to sidechains of Asp113, Glu153 and Thr186, and mainchain carbonyl oxygen of Thr148, may stabilize the leaving group, beta-phosphate of ATP.
(1) Asp235 acts as a general base to deprotonate 5'-hydroxyl group of pyridoxal, to activate it.
(2) The activated 5'-oxygen atom makes a nucleophilic attack on the gamma-phosphate of ATP, leading to the transition state. The transferred gamma-phosphate in the transition-state must be stabilized by an anion hole composed of mainchain amide groups of Gly232-Thr233-Gly234-Asp235, along with magnesium ion. The leaving group can be stabilized by the same magnesium ion and the potassium ion. Here, the reaction proceeds throuhg SN2-like mechanism.
(3) Finally, the transferrd gamma-phosphate is bonded to the 5'-oxygen of pyridoxal, to complete the raction.

createdupdated
2009-08-242012-01-12


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 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)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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