EzCatDB: M00198
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DB codeM00198
RLCP classification3.103.126600.1165 : Transfer
CATH domainDomain 1-.-.-.-
Domain 2-.-.-.-
Domain 33.30.200.20 : Phosphorylase Kinase; domain 1Catalytic domain
Domain 41.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 5-.-.-.-
Domain 61.10.238.10 : Recoverin; domain 1
Domain 71.10.238.10 : Recoverin; domain 1
E.C.2.7.11.19
CSA2phk
MACiEM0035

CATH domainRelated DB codes (homologues)
1.10.238.10 : Recoverin; domain 1M00183,D00151,M00118
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
3.30.200.20 : Phosphorylase Kinase; domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

P18688P12798P00518P62160
Protein namePhosphorylase b kinase regulatory subunit alpha, skeletal muscle isoformPhosphorylase b kinase regulatory subunit betaPhosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoformCalmodulinphosphorylase kinase
dephosphophosphorylase kinase
glycogen phosphorylase kinase
PHK
phosphorylase b kinase
phosphorylase B kinase
phosphorylase kinase (phosphorylating)
STK17
SynonymsPhosphorylase kinase alpha M subunit
Phosphorylase kinase subunit beta
EC 2.7.11.19
Phosphorylase kinase subunit gamma-1
Serine/threonine-protein kinase PHKG1
EC 2.7.11.1
EC 2.7.11.26
CaM
RefSeqNP_001159389.1 (Protein)
NM_001165917.1 (DNA/RNA sequence)
NP_001075770.1 (Protein)
NM_001082301.1 (DNA/RNA sequence)
NP_001095175.1 (Protein)
NM_001101705.1 (DNA/RNA sequence)
NP_001182569.1 (Protein)
NM_001195640.1 (DNA/RNA sequence)
PfamPF00723 (Glyco_hydro_15)
[Graphical view]
PF00723 (Glyco_hydro_15)
[Graphical view]
PF00069 (Pkinase)
[Graphical view]
PF13499 (EF_hand_5)
[Graphical view]


UniProtKB:Accession NumberP18688P12798P00518P62160
Entry nameKPB1_RABITKPBB_RABITPHKG1_RABITCALM_RABIT
Activity

2 ATP + phosphorylase b = 2 ADP + phosphorylase a.
SubunitPolymer of 16 chains, four each of alpha, beta, gamma, and delta. Alpha and beta are regulatory chains, gamma is the catalytic chain, and delta is calmodulin.Polymer of 16 chains, four each of alpha, beta, gamma, and delta. Alpha and beta are regulatory chains, gamma is the catalytic chain, and delta is calmodulin.Polymer of 16 chains, four each of alpha, beta, gamma, and delta. Alpha and beta are regulatory chains, gamma is the catalytic chain, and delta is calmodulin.Interacts with CEP97, CEP110, TTN/titin and SRY (By similarity).
Subcellular locationCell membrane, Lipid-anchor, Cytoplasmic side (Potential).Cell membrane, Lipid-anchor, Cytoplasmic side (Potential).
Spindle. Note=Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules (By similarity).
Cofactor




Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00076C00002C02308C00008C02307
CompoundMagnesiumCalciumATPPhosphorylase bADPPhosphorylase a
Typedivalent metal (Ca2+, Mg2+)divalent metal (Ca2+, Mg2+)amine group,nucleotidepeptide/proteinamine group,nucleotidepeptide/protein
ChEBI18420
29108
15422

16761

PubChem888
271
5957

6022

              
1phkA01UnboundUnboundAnalogue:ATPUnboundUnboundUnbound
1ql6A01UnboundUnboundAnalogue:ATPUnboundUnboundUnbound
2phkA01UnboundUnboundAnalogue:ATPUnboundUnboundUnbound
1phkA02Analogue:2x_MNUnboundUnboundUnboundUnboundUnbound
1ql6A02Analogue:2x_MNUnboundUnboundUnboundUnboundUnbound
2phkA02Analogue:2x_MNUnboundUnboundBound:ARG-GLN-MET-SER-PHE-ARG-LEU(chain B)UnboundUnbound

Active-site residues
resource
literature [8], [11], [14], [17]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1phkA01LYS 48
 
VAL 29
 
1ql6A01LYS 48
 
VAL 29
 
2phkA01LYS 48
 
VAL 29
 
1phkA02ASP 149;LYS 151
ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding)
 
 
1ql6A02ASP 149;LYS 151
ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding)
 
mutant E182S
2phkA02ASP 149;LYS 151
ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding)
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[11]Fig.6, p.6653-6655
[14]p.9-10
[17]Fig.7, p.14727-14729
[23]p.502-504

references
[1]
PubMed ID3967648
JournalEur J Biochem
Year1985
Volume146
Pages107-15
AuthorsHessova Z, Varsanyi M, Heilmeyer LM Jr
TitleDual function of calmodulin (delta) in phosphorylase kinase.
[2]
PubMed ID1931956
JournalBiochemistry
Year1991
Volume30
Pages10274-9
AuthorsFarrar YJ, Carlson GM
TitleKinetic characterization of the calmodulin-activated catalytic subunit of phosphorylase kinase.
[3]
PubMed ID1892899
JournalBiochim Biophys Acta
Year1991
Volume1094
Pages168-74
AuthorsHeilmeyer LM Jr
TitleMolecular basis of signal integration in phosphorylase kinase.
[4]
PubMed ID1731902
JournalBiochemistry
Year1992
Volume31
Pages437-42
AuthorsHenderson SJ, Newsholme P, Heidorn DB, Mitchell R, Seeger PA, Walsh DA, Trewhella J
TitleSolution structure of phosphorylase kinase studied using small-angle X-ray and neutron scattering.
[5]
PubMed ID8440701
JournalJ Biol Chem
Year1993
Volume268
Pages4120-5
AuthorsFarrar YJ, Lukas TJ, Craig TA, Watterson DM, Carlson GM
TitleFeatures of calmodulin that are important in the activation of the catalytic subunit of phosphorylase kinase.
[6]
PubMed ID8180216
JournalBiochemistry
Year1994
Volume33
Pages5877-83
AuthorsHuang CY, Yuan CJ, Luo S, Graves DJ
TitleMutational analyses of the metal ion and substrate binding sites of phosphorylase kinase gamma subunit.
[7]
CommentsCALMODULIN-BINDING DOMAINS.
PubMed ID7673209
JournalJ Biol Chem
Year1995
Volume270
Pages22283-9
AuthorsDasgupta M, Blumenthal DK
TitleCharacterization of the regulatory domain of the gamma-subunit of phosphorylase kinase. The two noncontiguous calmodulin-binding subdomains are also autoinhibitory.
Related UniProtKBP00518
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 15-291.
Medline ID95393018
PubMed ID7663944
JournalStructure
Year1995
Volume3
Pages467-82
AuthorsOwen DJ, Noble ME, Garman EF, Papageorgiou AC, Johnson LN
TitleTwo structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product.
Related PDB1phk
Related UniProtKBP00518
[9]
PubMed ID8664294
JournalBiochemistry
Year1996
Volume35
Pages5014-21
AuthorsXu YH, Wilkinson DA, Carlson GM
TitleDivalent cations but not other activators enhance phosphorylase kinase's affinity for glycogen phosphorylase.
[10]
PubMed ID8702882
JournalJ Biol Chem
Year1996
Volume271
Pages21126-33
AuthorsWangsgard WP, Meixell GE, Dasgupta M, Blumenthal DK
TitleActivation and inhibition of phosphorylase kinase by monospecific antibodies raised against peptides from the regulatory domain of the gamma-subunit.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 15-291.
Medline ID98031892
PubMed ID9362479
JournalEMBO J
Year1997
Volume16
Pages6646-58
AuthorsLowe ED, Noble ME, Skamnaki VT, Oikonomakos NG, Owen DJ, Johnson LN
TitleThe crystal structure of a phosphorylase kinase peptide substrate complex: kinase substrate recognition.
Related PDB2phk
Related UniProtKBP00518
[12]
PubMed ID9334188
JournalJ Biol Chem
Year1997
Volume272
Pages26202-9
AuthorsNadeau OW, Sacks DB, Carlson GM
TitleThe structural effects of endogenous and exogenous Ca2+/calmodulin on phosphorylase kinase.
[13]
PubMed ID9018046
JournalJ Mol Biol
Year1997
Volume265
Pages319-29
AuthorsWilkinson DA, Norcum MT, Fizgerald TJ, Marion TN, Tillman DM, Carlson GM
TitleProximal regions of the catalytic gamma and regulatory beta subunits on the interior lobe face of phosphorylase kinase are structurally coupled to each other and with enzyme activation.
[14]
PubMed ID9678585
JournalFEBS Lett
Year1998
Volume430
Pages1-11
AuthorsJohnson LN, Lowe ED, Noble ME, Owen DJ
TitleThe Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases.
[15]
PubMed ID10375405
JournalArch Biochem Biophys
Year1999
Volume367
Pages104-14
AuthorsPete MJ, Liao CX, Bartleson C, Graves DJ
TitleA recombinant form of the catalytic subunit of phosphorylase kinase that is soluble, monomeric, and includes key C-terminal residues.
[16]
PubMed ID10029550
JournalBiochemistry
Year1999
Volume38
Pages2551-9
AuthorsNadeau OW, Traxler KW, Fee LR, Baldwin BA, Carlson GM
TitleActivators of phosphorylase kinase alter the cross-linking of its catalytic subunit to the C-terminal one-sixth of its regulatory alpha subunit.
[17]
CommentsX-ray crystallography
PubMed ID10545198
JournalBiochemistry
Year1999
Volume38
Pages14718-30
AuthorsSkamnaki VT, Owen DJ, Noble ME, Lowe ED, Lowe G, Oikonomakos NG, Johnson LN
TitleCatalytic mechanism of phosphorylase kinase probed by mutational studies.
Related PDB1ql6
[18]
PubMed ID10487978
JournalFront Biosci
Year1999
Volume4
PagesD618-41
AuthorsBrushia RJ, Walsh DA
TitlePhosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure.
[19]
PubMed ID10333288
JournalJ Protein Chem
Year1999
Volume18
Pages157-64
AuthorsWilkinson DA, Fitzgerald TJ, Marion TN, Carlson GM
TitleMg2+ induces conformational changes in the catalytic subunit of phosphorylase kinase, whether by itself or as part of the holoenzyme complex.
[20]
PubMed ID10454193
JournalPharmacol Ther
Year1999
Volume82
Pages143-55
AuthorsGraves D, Bartleson C, Biorn A, Pete M
TitleSubstrate and inhibitor recognition of protein kinases: what is known about the catalytic subunit of phosphorylase kinase?
[21]
PubMed ID11004553
JournalBiochim Biophys Acta
Year2000
Volume1480
Pages23-8
AuthorsBartleson C, Luo S, Graves DJ, Martin BL
TitleArginine to citrulline replacement in substrates of phosphorylase kinase.
[22]
PubMed ID10976872
JournalCell Mol Biol (Noisy-le-grand)
Year2000
Volume46
Pages883-94
AuthorsWilmann M, Gautel M, Mayans O
TitleActivation of calcium/calmodulin regulated kinases.
[23]
PubMed ID11195974
JournalJ Protein Chem
Year2000
Volume19
Pages499-505
AuthorsSkamnaki VT, Oikonomakos NG
TitleKinetic characterization of the double mutant R148A/E182S of glycogen phosphorylase kinase catalytic subunit: the role of the activation loop.
[24]
PubMed ID11448955
JournalJ Biol Chem
Year2001
Volume276
Pages34560-6
AuthorsBartleson C, Graves DJ
TitleAn inhibitory segment of the catalytic subunit of phosphorylase kinase does not act as a pseudosubstrate.
[25]
PubMed ID12460118
JournalBiochemistry (Mosc)
Year2002
Volume67
Pages1197-202
AuthorsAndreeva IE, Rice NA, Carlson GM
TitleThe regulatory alpha subunit of phosphorylase kinase may directly participate in the binding of glycogen phosphorylase.
[26]
PubMed ID11847235
JournalJ Biol Chem
Year2002
Volume277
Pages14681-7
AuthorsRice NA, Nadeau OW, Yang Q, Carlson GM
TitleThe calmodulin-binding domain of the catalytic gamma subunit of phosphorylase kinase interacts with its inhibitory alpha subunit: evidence for a Ca2+ sensitive network of quaternary interactions.
[27]
PubMed ID11796107
JournalStructure
Year2002
Volume10
Pages23-32
AuthorsNadeau OW, Carlson GM, Gogol EP
TitleA Ca(2+)-dependent global conformational change in the 3D structure of phosphorylase kinase obtained from electron microscopy.
[28]
PubMed ID11796108
JournalStructure
Year2002
Volume10
Pages33-41
AuthorsVenien-Bryan C, Lowe EM, Boisset N, Traxler KW, Johnson LN, Carlson GM
TitleThree-dimensional structure of phosphorylase kinase at 22 A resolution and its complex with glycogen phosphorylase b.
[29]
PubMed ID12876330
JournalProtein Sci
Year2003
Volume12
Pages1804-7
AuthorsPallen MJ
TitleGlucoamylase-like domains in the alpha- and beta-subunits of phosphorylase kinase.
[30]
PubMed ID15752366
JournalFEBS J
Year2005
Volume272
Pages1511-22
AuthorsCook AG, Johnson LN, McDonnell JM
TitleStructural characterization of Ca2+/CaM in complex with the phosphorylase kinase PhK5 peptide.
[31]
PubMed ID15741333
JournalProtein Sci
Year2005
Volume14
Pages1039-48
AuthorsPriddy TS, MacDonald BA, Heller WT, Nadeau OW, Trewhella J, Carlson GM
TitleCa2+-induced structural changes in phosphorylase kinase detected by small-angle X-ray scattering.

comments
The E.C. was transferred from 2.7.1.38 to 2.7.11.19 in 2005.
This enzyme is composed 16 subunits, four each of alpha, beta, gamma, and delta.
The structure of the C-terminal region of catalytic gamma subunit has not been determined. This C-terminal region has two calmodulin binding sites.
Although it is not described in KEGG nor swiss-prot, calcium (C00076) is included as a cofactor, it is not involved in catalysis. Calcium ions bind to delta subunit (calmodulin) and regulate activity of catalytic subunits.
The catalytic domains of this enzyme similar to those of other protein kinases (D00114, T00224, M00125, M00195, M00197 in EzCatDB).
This enzyme catalyzes the following reaction (see [17]):
(0) Lys151 stabilizes the transferred group, gamma-phosphate of ATP, whereas Lys48 stabilizes the leaving group, alpha- and beta-phosphate groups. Moreover, magnesium ion bound to Asn154 and Asp167 stabilizes the transferred group and leaving group, beta- and gamma-phosphate groups, along with the mainchain amide group of Val29.
(1) Asp149 acts as a general base to deprotonate and activate the acceptor group, hydroxyl group of the substrate seryl group.
(2) The bond-breaking of the transferred group, the gamma-phosphate, from the leaving group, beta,gamma-bridging oxygen of ATP occurs in advance of the incoming nucleophile (the activated hydroxyl group) (SN1-like mechanism).
(3) The activated hydroxyl oxygen makes a nucleophilic attack on the gamma-phosphate group, forming a new covalent bond.
(4) Asp149 acts as a general acid to protonate the transferred group, the gamma-phosphate group.

createdupdated
2007-07-122009-02-26


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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