DB code: M00198

RLCP classification 3.103.126600.1165 : Transfer
CATH domain -.-.-.- :
-.-.-.- :
3.30.200.20 : Phosphorylase Kinase; domain 1 Catalytic domain
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
-.-.-.- :
1.10.238.10 : Recoverin; domain 1
1.10.238.10 : Recoverin; domain 1
E.C. 2.7.11.19
CSA 2phk
M-CSA 2phk
MACiE M0035

CATH domain Related DB codes (homologues)
1.10.238.10 : Recoverin; domain 1 M00183 D00151 M00118
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 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 1 M00125 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P18688 Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform
Phosphorylase kinase alpha M subunit
NP_001159389.1 (Protein)
NM_001165917.1 (DNA/RNA sequence)
PF00723 (Glyco_hydro_15)
[Graphical View]
P12798 Phosphorylase b kinase regulatory subunit beta
Phosphorylase kinase subunit beta
NP_001075770.1 (Protein)
NM_001082301.1 (DNA/RNA sequence)
PF00723 (Glyco_hydro_15)
[Graphical View]
P00518 Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform
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
NP_001095175.1 (Protein)
NM_001101705.1 (DNA/RNA sequence)
PF00069 (Pkinase)
[Graphical View]
P62160 Calmodulin
CaM
NP_001182569.1 (Protein)
NM_001195640.1 (DNA/RNA sequence)
PF13499 (EF_hand_5)
[Graphical View]

KEGG enzyme name
phosphorylase kinase
dephosphophosphorylase kinase
glycogen phosphorylase kinase
PHK
phosphorylase b kinase
phosphorylase B kinase
phosphorylase kinase (phosphorylating)
STK17

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P18688 KPB1_RABIT 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. Cell membrane, Lipid-anchor, Cytoplasmic side (Potential).
P12798 KPBB_RABIT 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. Cell membrane, Lipid-anchor, Cytoplasmic side (Potential).
P00518 PHKG1_RABIT 2 ATP + phosphorylase b = 2 ADP + phosphorylase a. 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.
P62160 CALM_RABIT Interacts with CEP97, CEP110, TTN/titin and SRY (By similarity). Spindle. Note=Distributed throughout the cell during interphase, but during mitosis becomes dramatically localized to the spindle poles and the spindle microtubules (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00076 C00002 C02308 C00008 C02307
E.C.
Compound Magnesium Calcium ATP Phosphorylase b ADP Phosphorylase a
Type divalent metal (Ca2+, Mg2+) divalent metal (Ca2+, Mg2+) amine group,nucleotide peptide/protein amine group,nucleotide peptide/protein
ChEBI 18420
 18420
 		29108
 29108
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		271
 271
 		5957
 5957
 		6022
 6022
1phkA01 Unbound Unbound Analogue:ATP Unbound Unbound Unbound
1ql6A01 Unbound Unbound Analogue:ATP Unbound Unbound Unbound
2phkA01 Unbound Unbound Analogue:ATP Unbound Unbound Unbound
1phkA02 Analogue:2x_MN Unbound Unbound Unbound Unbound Unbound
1ql6A02 Analogue:2x_MN Unbound Unbound Unbound Unbound Unbound
2phkA02 Analogue:2x_MN Unbound Unbound Bound:ARG-GLN-MET-SER-PHE-ARG-LEU(chain B) Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [8], [11], [14], [17]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1phkA01 LYS 48 VAL 29
1ql6A01 LYS 48 VAL 29
2phkA01 LYS 48 VAL 29
1phkA02 ASP 149;LYS 151 ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding)
1ql6A02 ASP 149;LYS 151 ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding) mutant E182S
2phkA02 ASP 149;LYS 151 ASN 154(Magnesium-1 binding);ASP 167(Magnesium-1 & -2 binding)

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 3967648
Journal Eur J Biochem
Year 1985
Volume 146
Pages 107-15
Authors Hessova Z, Varsanyi M, Heilmeyer LM Jr
Title Dual function of calmodulin (delta) in phosphorylase kinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1931956
Journal Biochemistry
Year 1991
Volume 30
Pages 10274-9
Authors Farrar YJ, Carlson GM
Title Kinetic characterization of the calmodulin-activated catalytic subunit of phosphorylase kinase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1892899
Journal Biochim Biophys Acta
Year 1991
Volume 1094
Pages 168-74
Authors Heilmeyer LM Jr
Title Molecular basis of signal integration in phosphorylase kinase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1731902
Journal Biochemistry
Year 1992
Volume 31
Pages 437-42
Authors Henderson SJ, Newsholme P, Heidorn DB, Mitchell R, Seeger PA, Walsh DA, Trewhella J
Title Solution structure of phosphorylase kinase studied using small-angle X-ray and neutron scattering.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8440701
Journal J Biol Chem
Year 1993
Volume 268
Pages 4120-5
Authors Farrar YJ, Lukas TJ, Craig TA, Watterson DM, Carlson GM
Title Features of calmodulin that are important in the activation of the catalytic subunit of phosphorylase kinase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8180216
Journal Biochemistry
Year 1994
Volume 33
Pages 5877-83
Authors Huang CY, Yuan CJ, Luo S, Graves DJ
Title Mutational analyses of the metal ion and substrate binding sites of phosphorylase kinase gamma subunit.
Related PDB
Related UniProtKB
[7]
Resource
Comments CALMODULIN-BINDING DOMAINS.
Medline ID
PubMed ID 7673209
Journal J Biol Chem
Year 1995
Volume 270
Pages 22283-9
Authors Dasgupta M, Blumenthal DK
Title Characterization of the regulatory domain of the gamma-subunit of phosphorylase kinase. The two noncontiguous calmodulin-binding subdomains are also autoinhibitory.
Related PDB
Related UniProtKB P00518
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 15-291.
Medline ID 95393018
PubMed ID 7663944
Journal Structure
Year 1995
Volume 3
Pages 467-82
Authors Owen DJ, Noble ME, Garman EF, Papageorgiou AC, Johnson LN
Title Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product.
Related PDB 1phk
Related UniProtKB P00518
[9]
Resource
Comments
Medline ID
PubMed ID 8664294
Journal Biochemistry
Year 1996
Volume 35
Pages 5014-21
Authors Xu YH, Wilkinson DA, Carlson GM
Title Divalent cations but not other activators enhance phosphorylase kinase's affinity for glycogen phosphorylase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8702882
Journal J Biol Chem
Year 1996
Volume 271
Pages 21126-33
Authors Wangsgard WP, Meixell GE, Dasgupta M, Blumenthal DK
Title Activation and inhibition of phosphorylase kinase by monospecific antibodies raised against peptides from the regulatory domain of the gamma-subunit.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 15-291.
Medline ID 98031892
PubMed ID 9362479
Journal EMBO J
Year 1997
Volume 16
Pages 6646-58
Authors Lowe ED, Noble ME, Skamnaki VT, Oikonomakos NG, Owen DJ, Johnson LN
Title The crystal structure of a phosphorylase kinase peptide substrate complex: kinase substrate recognition.
Related PDB 2phk
Related UniProtKB P00518
[12]
Resource
Comments
Medline ID
PubMed ID 9334188
Journal J Biol Chem
Year 1997
Volume 272
Pages 26202-9
Authors Nadeau OW, Sacks DB, Carlson GM
Title The structural effects of endogenous and exogenous Ca2+/calmodulin on phosphorylase kinase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9018046
Journal J Mol Biol
Year 1997
Volume 265
Pages 319-29
Authors Wilkinson DA, Norcum MT, Fizgerald TJ, Marion TN, Tillman DM, Carlson GM
Title Proximal 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.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9678585
Journal FEBS Lett
Year 1998
Volume 430
Pages 1-11
Authors Johnson LN, Lowe ED, Noble ME, Owen DJ
Title The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10375405
Journal Arch Biochem Biophys
Year 1999
Volume 367
Pages 104-14
Authors Pete MJ, Liao CX, Bartleson C, Graves DJ
Title A recombinant form of the catalytic subunit of phosphorylase kinase that is soluble, monomeric, and includes key C-terminal residues.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10029550
Journal Biochemistry
Year 1999
Volume 38
Pages 2551-9
Authors Nadeau OW, Traxler KW, Fee LR, Baldwin BA, Carlson GM
Title Activators of phosphorylase kinase alter the cross-linking of its catalytic subunit to the C-terminal one-sixth of its regulatory alpha subunit.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10545198
Journal Biochemistry
Year 1999
Volume 38
Pages 14718-30
Authors Skamnaki VT, Owen DJ, Noble ME, Lowe ED, Lowe G, Oikonomakos NG, Johnson LN
Title Catalytic mechanism of phosphorylase kinase probed by mutational studies.
Related PDB 1ql6
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10487978
Journal Front Biosci
Year 1999
Volume 4
Pages D618-41
Authors Brushia RJ, Walsh DA
Title Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10333288
Journal J Protein Chem
Year 1999
Volume 18
Pages 157-64
Authors Wilkinson DA, Fitzgerald TJ, Marion TN, Carlson GM
Title Mg2+ induces conformational changes in the catalytic subunit of phosphorylase kinase, whether by itself or as part of the holoenzyme complex.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10454193
Journal Pharmacol Ther
Year 1999
Volume 82
Pages 143-55
Authors Graves D, Bartleson C, Biorn A, Pete M
Title Substrate and inhibitor recognition of protein kinases: what is known about the catalytic subunit of phosphorylase kinase?
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11004553
Journal Biochim Biophys Acta
Year 2000
Volume 1480
Pages 23-8
Authors Bartleson C, Luo S, Graves DJ, Martin BL
Title Arginine to citrulline replacement in substrates of phosphorylase kinase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10976872
Journal Cell Mol Biol (Noisy-le-grand)
Year 2000
Volume 46
Pages 883-94
Authors Wilmann M, Gautel M, Mayans O
Title Activation of calcium/calmodulin regulated kinases.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11195974
Journal J Protein Chem
Year 2000
Volume 19
Pages 499-505
Authors Skamnaki VT, Oikonomakos NG
Title Kinetic characterization of the double mutant R148A/E182S of glycogen phosphorylase kinase catalytic subunit: the role of the activation loop.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11448955
Journal J Biol Chem
Year 2001
Volume 276
Pages 34560-6
Authors Bartleson C, Graves DJ
Title An inhibitory segment of the catalytic subunit of phosphorylase kinase does not act as a pseudosubstrate.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12460118
Journal Biochemistry (Mosc)
Year 2002
Volume 67
Pages 1197-202
Authors Andreeva IE, Rice NA, Carlson GM
Title The regulatory alpha subunit of phosphorylase kinase may directly participate in the binding of glycogen phosphorylase.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 11847235
Journal J Biol Chem
Year 2002
Volume 277
Pages 14681-7
Authors Rice NA, Nadeau OW, Yang Q, Carlson GM
Title The 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.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 11796107
Journal Structure
Year 2002
Volume 10
Pages 23-32
Authors Nadeau OW, Carlson GM, Gogol EP
Title A Ca(2+)-dependent global conformational change in the 3D structure of phosphorylase kinase obtained from electron microscopy.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11796108
Journal Structure
Year 2002
Volume 10
Pages 33-41
Authors Venien-Bryan C, Lowe EM, Boisset N, Traxler KW, Johnson LN, Carlson GM
Title Three-dimensional structure of phosphorylase kinase at 22 A resolution and its complex with glycogen phosphorylase b.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12876330
Journal Protein Sci
Year 2003
Volume 12
Pages 1804-7
Authors Pallen MJ
Title Glucoamylase-like domains in the alpha- and beta-subunits of phosphorylase kinase.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 15752366
Journal FEBS J
Year 2005
Volume 272
Pages 1511-22
Authors Cook AG, Johnson LN, McDonnell JM
Title Structural characterization of Ca2+/CaM in complex with the phosphorylase kinase PhK5 peptide.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 15741333
Journal Protein Sci
Year 2005
Volume 14
Pages 1039-48
Authors Priddy TS, MacDonald BA, Heller WT, Nadeau OW, Trewhella J, Carlson GM
Title Ca2+-induced structural changes in phosphorylase kinase detected by small-angle X-ray scattering.
Related PDB
Related UniProtKB

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.

Created Updated
2007-07-12 2009-02-26