DB code: M00043

RLCP classification 3.103.106000.1163 : Transfer
CATH domain 3.10.20.90 : Ubiquitin-like (UB roll)
2.60.40.150 : Immunoglobulin-like
1.25.40.70 : Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat
3.30.1010.10 : Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4 Catalytic domain
1.10.1070.11 : Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5 Catalytic domain
2.30.30.40 : SH3 type barrels.
1.10.555.10 : Phosphatidylinositol 3-kinase; Chain A
3.30.505.10 : SHC Adaptor Protein
3.30.505.10 : SHC Adaptor Protein
E.C. 2.7.1.153
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.30.30.40 : SH3 type barrels. M00183 M00130 T00256 M00304 M00335
2.60.40.150 : Immunoglobulin-like M00221 M00183 M00118
3.30.505.10 : SHC Adaptor Protein M00183 M00130 M00148 T00256 M00304 M00333 M00339 M00344 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P32871 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
PI3-kinase subunit alpha
PI3K-alpha
PI3Kalpha
PtdIns-3-kinase subunit alpha
EC 2.7.1.153
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha
PtdIns-3-kinase subunit p110-alpha
p110alpha
Phosphoinositide-3-kinase catalytic alpha polypeptide
Serine/threonine protein kinase PIK3CA
EC 2.7.11.1
NP_776999.1 (Protein)
NM_174574.1 (DNA/RNA sequence)
PF00454 (PI3_PI4_kinase)
PF00792 (PI3K_C2)
PF02192 (PI3K_p85B)
PF00794 (PI3K_rbd)
PF00613 (PI3Ka)
[Graphical View]
O02697 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
PI3-kinase subunit gamma
PI3K-gamma
PI3Kgamma
PtdIns-3-kinase subunit gamma
EC 2.7.1.153
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma
PtdIns-3-kinase subunit p110-gamma
p110gamma
Phosphoinositide-3-kinase catalytic gamma polypeptide
Serine/threonine protein kinase PIK3CG
EC 2.7.11.1
p120-PI3K
NP_999104.1 (Protein)
NM_213939.1 (DNA/RNA sequence)
PF00454 (PI3_PI4_kinase)
PF00792 (PI3K_C2)
PF00794 (PI3K_rbd)
PF00613 (PI3Ka)
[Graphical View]
P48736 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
PI3-kinase subunit gamma
PI3K-gamma
PI3Kgamma
PtdIns-3-kinase subunit gamma
EC 2.7.1.153
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma
PtdIns-3-kinase subunit p110-gamma
p110gamma
Phosphoinositide-3-kinase catalytic gamma polypeptide
Serine/threonine protein kinase PIK3CG
EC 2.7.11.1
p120-PI3K
NP_002640.2 (Protein)
NM_002649.2 (DNA/RNA sequence)
PF00454 (PI3_PI4_kinase)
PF00792 (PI3K_C2)
PF00794 (PI3K_rbd)
PF00613 (PI3Ka)
[Graphical View]
P23727 Phosphatidylinositol 3-kinase regulatory subunit alpha
PI3-kinase regulatory subunit alpha
PI3K regulatory subunit alpha
PtdIns-3-kinase regulatory subunit alpha
Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
PI3-kinase subunit p85-alpha
PtdIns-3-kinase regulatory subunit p85-alpha
NP_777000.1 (Protein)
NM_174575.1 (DNA/RNA sequence)
PF00620 (RhoGAP)
PF00017 (SH2)
PF07653 (SH3_2)
[Graphical View]
P27986 Phosphatidylinositol 3-kinase regulatory subunit alpha
PI3-kinase regulatory subunit alpha
PI3K regulatory subunit alpha
PtdIns-3-kinase regulatory subunit alpha
Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
PI3-kinase subunit p85-alpha
PtdIns-3-kinase regulatory subunit p85-alpha
NP_001229395.1 (Protein)
NM_001242466.1 (DNA/RNA sequence)
NP_852556.2 (Protein)
NM_181504.3 (DNA/RNA sequence)
NP_852664.1 (Protein)
NM_181523.2 (DNA/RNA sequence)
NP_852665.1 (Protein)
NM_181524.1 (DNA/RNA sequence)
PF00620 (RhoGAP)
PF00017 (SH2)
PF07653 (SH3_2)
[Graphical View]

KEGG enzyme name
phosphatidylinositol-4,5-bisphosphate 3-kinase
type I phosphoinositide 3-kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P32871 PK3CA_BOVIN ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit. Binds to IRS1 in nuclear extracts. Interacts with RUFY3 (By similarity).
O02697 PK3CG_PIG ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit.
P48736 PK3CG_HUMAN ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate. Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit.
P23727 P85A_BOVIN Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits. Interacts with phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or BCR activation. Interacts with CBLB. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST (By similarity).
P27986 P85A_HUMAN Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits. Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with SOCS7. Interacts with RUFY3 (By similarity). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. Interacts with CBLB. Interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK). This interaction depends on the C- terminus of both proteins and leads to increased production of HIV. Interacts with HCV NS5A. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with IRS1 and phosphorylated IRS4, as well as with NISCH and HCST.

KEGG Pathways
Map code Pathways E.C.
MAP04070 Phosphatidylinositol signaling system
MAP00562 Inositol phosphate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C04637 C00008 C05981
E.C.
Compound Magnesium ATP 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate ADP 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide carbohydrate,lipid,phosphate group/phosphate ion amine group,nucleotide carbohydrate,lipid,phosphate group/phosphate ion
ChEBI 18420
15422
16761
PubChem 888
5957
6022
1e7uA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7vA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8wA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8xA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e90A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qmmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8yA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1he8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7uA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7vA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8wA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8xA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e90A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qmmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8yA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1he8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7uA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7vA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8wA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8xA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e90A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qmmA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8yA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8zA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1he8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7uA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:KWT Unbound Unbound
1e7vA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8wA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8xA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:ATP Unbound Unbound Unbound
1e90A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qmmA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:ATP Unbound Unbound Unbound
1e8yA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8zA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1he8A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7uA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e7vA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8wA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8xA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_LU Unbound Unbound Unbound Unbound
1e90A05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qmmA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_LU Unbound Unbound Unbound Unbound
1e8yA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1e8zA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1he8A05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pnjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2pniA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1phtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pksA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pktA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pbwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1pbwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1oo3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1oo4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2pnaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2pnbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bfiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bfjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1qadA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1h9oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1picA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
(See comments)

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1e7uA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e7vA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8wA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8xA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e90A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qmmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8yA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1he8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e7uA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e7vA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e8wA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e8xA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e90A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1qmmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e8yA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant P1M
1e8zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant P1M
1he8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant R505A
1e7uA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e7vA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8wA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8xA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e90A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qmmA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8yA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e8zA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1he8A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1e7uA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e7vA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e8wA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e8xA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e90A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1qmmA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e8yA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e8zA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1he8A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 806;LYS 807;LYS 833 ASP 836(Magnesium binding)
1e7uA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e7vA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e8wA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e8xA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e90A05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1qmmA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e8yA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1e8zA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1he8A05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 948;ASP 950 ASN 951;ASP 964(Magnesium binding)
1pnjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2pniA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1phtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pksA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pktA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pbwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pbwB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1oo3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1oo4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2pnaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2pnbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bfiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bfjA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1qadA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1h9oA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1picA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[29]
p.315
[46]
p.428-429

References
[1]
Resource
Comments STRUCTURE BY NMR OF 314-431
Medline ID 92357146
PubMed ID 1323062
Journal Nature
Year 1992
Volume 358
Pages 684-7
Authors Booker GW, Breeze AL, Downing AK, Panayotou G, Gout I, Waterfield MD, Campbell ID
Title Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase.
Related PDB 2pna 2pnb
Related UniProtKB P23727
[2]
Resource
Comments CIRCULAR DICHROISM AND FLUORESCENCE SPECTROSCOPY
Medline ID 93049176
PubMed ID 1330535
Journal EMBO J
Year 1992
Volume 11
Pages 4261-72
Authors Panayotou G, Bax B, Gout I, Federwisch M, Wroblowski B, Dhand R, Fry MJ, Blundell TL, Wollmer A, Waterfield MD
Title Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes.
Related PDB
Related UniProtKB P23727
[3]
Resource
Comments STRUCTURE BY NMR OF 1-84
Medline ID 93272320
PubMed ID 7684655
Journal Cell
Year 1993
Volume 73
Pages 813-22
Authors Booker GW, Gout I, Downing AK, Driscoll PC, Boyd J, Waterfield MD, Campbell ID
Title Solution structure and ligand-binding site of the SH3 domain of the p85 alpha subunit of phosphatidylinositol 3-kinase.
Related PDB 1pnj 2pni
Related UniProtKB P23727
[4]
Resource
Comments STRUCTURE BY NMR OF 1-79
Medline ID 93208889
PubMed ID 7681364
Journal Cell
Year 1993
Volume 72
Pages 945-52
Authors Koyama S, Yu H, Dalgarno DC, Shin TB, Zydowsky LD, Schreiber SL
Title Structure of the PI3K SH3 domain and analysis of the SH3 family.
Related PDB 1pks 1pkt
Related UniProtKB P27986
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 115-298
Medline ID 97121392
PubMed ID 8962058
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 14373-8
Authors Musacchio A, Cantley LC, Harrison SC
Title Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit.
Related PDB 1pbw
Related UniProtKB P27986
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 324-434
Medline ID 96185448
PubMed ID 8599763
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 364-74
Authors Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC
Title Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes.
Related PDB
Related UniProtKB P27986
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-85
Medline ID 96196433
PubMed ID 8648629
Journal J Mol Biol
Year 1996
Volume 257
Pages 632-43
Authors Liang J, Chen JK, Schreiber ST, Clardy J
Title Crystal structure of P13K SH3 domain at 20 angstroms resolution.
Related PDB 1pht
Related UniProtKB P27986
[8]
Resource
Comments STRUCTURE BY NMR OF 617-724
Medline ID 96312955
PubMed ID 8670861
Journal EMBO J
Year 1996
Volume 15
Pages 3579-89
Authors Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA
Title Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase.
Related PDB 1pic
Related UniProtKB P27986
[9]
Resource
Comments STRUCTURE BY NMR OF 321-434
Medline ID 97110350
PubMed ID 8952511
Journal Biochemistry
Year 1996
Volume 35
Pages 15570-81
Authors Gunther UL, Liu Y, Sanford D, Bachovchin WW, Schaffhausen B
Title NMR analysis of interactions of a phosphatidylinositol 3'-kinase SH2 domain with phosphotyrosine peptides reveals interdependence of major binding sites.
Related PDB
Related UniProtKB P23727
[10]
Resource
Comments STRUCTURE BY NMR OF 91-104
Medline ID 97121261
PubMed ID 8961927
Journal Biochemistry
Year 1996
Volume 35
Pages 15646-53
Authors Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE
Title Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase.
Related PDB
Related UniProtKB P27986
[11]
Resource
Comments VARIANT ILE-326
Medline ID 97184306
PubMed ID 9032108
Journal Diabetes
Year 1997
Volume 46
Pages 494-501
Authors Hansen T, Andersen CB, Echwald SM, Urhammer SA, Clausen JO, Vestergaard H, Owens D, Hansen L, Pedersen O
Title Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index.
Related PDB
Related UniProtKB P27986
[12]
Resource
Comments
Medline ID
PubMed ID 9034995
Journal J Rheumatol
Year 1997
Volume 24
Pages 341-8
Authors Jackson JK, Lauener R, Duronio V, Burt HM
Title The involvement of phosphatidylinositol 3-kinase in crystal induced human neutrophil activation.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9391111
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 13820-5
Authors Li Z, Wahl MI, Eguinoa A, Stephens LR, Hawkins PT, Witte ON
Title Phosphatidylinositol 3-kinase-gamma activates Bruton's tyrosine kinase in concert with Src family kinases.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9488453
Journal Mol Cell Biol
Year 1998
Volume 18
Pages 1379-87
Authors Yu J, Zhang Y, McIlroy J, Rordorf-Nikolic T, Orr GA, Backer JM
Title Regulation of the p85/p110 phosphatidylinositol 3'-kinase: stabilization and inhibition of the p110alpha catalytic subunit by the p85 regulatory subunit.
Related PDB
Related UniProtKB
[15]
Resource
Comments STRUCTURE BY NMR OF 614-724
Medline ID 98173872
PubMed ID 9512716
Journal J Mol Biol
Year 1998
Volume 276
Pages 461-78
Authors Siegal G, Davis B, Kristensen SM, Sankar A, Linacre J, Stein RC, Panayotou G, Waterfield MD, Driscoll PC
Title Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory subunit of phosphoinositide 3-kinase.
Related PDB 1bfi 1bfj
Related UniProtKB P23727
[16]
Resource
Comments
Medline ID
PubMed ID 9461588
Journal J Biol Chem
Year 1998
Volume 273
Pages 3994-4000
Authors von Willebrand M, Williams S, Saxena M, Gilman J, Tailor P, Jascur T, Amarante-Mendes GP, Green DR, Mustelin T
Title Modification of phosphatidylinositol 3-kinase SH2 domain binding properties by Abl- or Lck-mediated tyrosine phosphorylation at Tyr-688.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9804776
Journal J Biol Chem
Year 1998
Volume 273
Pages 30199-203
Authors Yu J, Wjasow C, Backer JM
Title Regulation of the p85/p110alpha phosphatidylinositol 3'-kinase. Distinct roles for the n-terminal and c-terminal SH2 domains.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9677338
Journal Biochem J
Year 1998
Volume 333
Pages 757-63
Authors Hellyer NJ, Cheng K, Koland JG
Title ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9551103
Journal J Mol Biol
Year 1998
Volume 276
Pages 657-67
Authors Guijarro JI, Morton CJ, Plaxco KW, Campbell ID, Dobson CM
Title Folding kinetics of the SH3 domain of PI3 kinase by real-time NMR combined with optical spectroscopy.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9539718
Journal Proc Natl Acad Sci U S A
Year 1998
Volume 95
Pages 4224-8
Authors Guijarro JI, Sunde M, Jones JA, Campbell ID, Dobson CM
Title Amyloid fibril formation by an SH3 domain.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9593201
Journal Proteins
Year 1998
Volume 31
Pages 309-19
Authors Knapp S, Mattson PT, Christova P, Berndt KD, Karshikoff A, Vihinen M, Smith CI, Ladenstein R
Title Thermal unfolding of small proteins with SH3 domain folding pattern.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9765155
Journal Science
Year 1998
Volume 282
Pages 293-6
Authors Bondeva T, Pirola L, Bulgarelli-Leva G, Rubio I, Wetzker R, Wymann MP
Title Bifurcation of lipid and protein kinase signals of PI3Kgamma to the protein kinases PKB and MAPK.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10525402
Journal J Mol Biol
Year 1999
Volume 292
Pages 763-70
Authors Hoedemaeker FJ, Siegal G, Roe SM, Driscoll PC, Abrahams JP
Title Crystal structure of the C-terminal SH2 domain of the p85alpha regulatory subunit of phosphoinositide 3-kinase: an SH2 domain mimicking its own substrate.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10358930
Journal Chem Phys Lipids
Year 1999
Volume 98
Pages 79-86
Authors Katada T, Kurosu H, Okada T, Suzuki T, Tsujimoto N, Takasuga S, Kontani K, Hazeki O, Ui M
Title Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10022824
Journal EMBO J
Year 1999
Volume 18
Pages 815-21
Authors Jimenez JL, Guijarro JI, Orlova E, Zurdo J, Dobson CM, Sunde M, Saibil HR
Title Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10212202
Journal J Biol Chem
Year 1999
Volume 274
Pages 12323-32
Authors Harpur AG, Layton MJ, Das P, Bottomley MJ, Panayotou G, Driscoll PC, Waterfield MD
Title Intermolecular interactions of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10356365
Journal Mol Cell Biol Res Commun
Year 1999
Volume 1
Pages 153-7
Authors Beeton CA, Das P, Waterfield MD, Shepherd PR
Title The SH3 and BH domains of the p85alpha adapter subunit play a critical role in regulating class Ia phosphoinositide 3-kinase function.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 10358071
Journal J Biol Chem
Year 1999
Volume 274
Pages 17152-8
Authors Krugmann S, Hawkins PT, Pryer N, Braselmann S
Title Characterizing the interactions between the two subunits of the p101/p110gamma phosphoinositide 3-kinase and their role in the activation of this enzyme by G beta gamma subunits.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 10580505
Journal Nature
Year 1999
Volume 402
Pages 313-20
Authors Walker EH, Perisic O, Ried C, Stephens L, Williams RL
Title Structural insights into phosphoinositide 3-kinase catalysis and signalling. PDB;1qmm
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 10835283
Journal J Mol Biol
Year 2000
Volume 299
Pages 771-88
Authors Kristensen SM, Siegal G, Sankar A, Driscoll PC
Title Backbone dynamics of the C-terminal SH2 domain of the p85alpha subunit of phosphoinositide 3-kinase: effect of phosphotyrosine-peptide binding and characterization of slow conformational exchange processes.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 10967104
Journal J Biol Chem
Year 2000
Volume 275
Pages 36450-6
Authors King TR, Fang Y, Mahon ES, Anderson DH
Title Using a phage display library to identify basic residues in A-Raf required to mediate binding to the Src homology 2 domains of the p85 subunit of phosphatidylinositol 3'-kinase.
Related PDB
Related UniProtKB
[32]
Resource
Comments VARIANT INSULIN RESISTANCE GLN-409, AND VARIANT ILE-326
Medline ID 20230645
PubMed ID 10768093
Journal Diabetologia
Year 2000
Volume 43
Pages 321-31
Authors Baynes KC, Beeton CA, Panayotou G, Stein R, Soos M, Hansen T, Simpson H, O'Rahilly S, Shepherd PR, Whitehead JP
Title Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity.
Related PDB
Related UniProtKB P27986
[33]
Resource
Comments
Medline ID
PubMed ID 11123912
Journal Biochemistry
Year 2000
Volume 39
Pages 15860-9
Authors Weber T, Schaffhausen B, Liu Y, Gunther UL
Title NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 10861385
Journal Biopolymers
Year 2000
Volume 57
Pages 208-17
Authors Okishio N, Nagai M, Fukuda R, Nagatomo S, Kitagawa T
Title Interactions of phosphatidylinositol 3-kinase Src homology 3 domain with its ligand peptide studied by absorption, circular dichroism, and UV resonance raman spectroscopies.
Related PDB
Related UniProtKB
[35]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11136978
Journal Cell
Year 2000
Volume 103
Pages 931-43
Authors Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL
Title Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma.
Related PDB 1he8
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 11067939
Journal J Immunol
Year 2000
Volume 165
Pages 5798-806
Authors Tudan C, Jackson JK, Blanis L, Pelech SL, Burt HM
Title Inhibition of TNF-alpha-induced neutrophil apoptosis by crystals of calcium pyrophosphate dihydrate is mediated by the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways up-stream of caspase 3.
Related PDB
Related UniProtKB
[37]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11090628
Journal Mol Cell
Year 2000
Volume 6
Pages 909-19
Authors Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL
Title Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine.
Related PDB 1e7u 1e7v 1e8w 1e8x 1e8y 1e8z 1e90 1qmm
Related UniProtKB
[38]
Resource
Comments
Medline ID
PubMed ID 11418612
Journal J Biol Chem
Year 2001
Volume 276
Pages 36174-82
Authors Gelkop S, Babichev Y, Isakov N
Title T cell activation induces direct binding of the Crk adapter protein to the regulatory subunit of phosphatidylinositol 3-kinase (p85) via a complex mechanism involving the Cbl protein.
Related PDB
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 11567151
Journal Acta Crystallogr D Biol Crystallogr
Year 2001
Volume 57
Pages 1397-404
Authors Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN
Title NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex.
Related PDB 1h9o
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 11141062
Journal Biochemistry
Year 2001
Volume 40
Pages 119-29
Authors Okishio N, Tanaka T, Fukuda R, Nagai M
Title Role of the conserved acidic residue Asp21 in the structure of phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and nuclear magnetic resonance studies.
Related PDB
Related UniProtKB
[41]
Resource
Comments
Medline ID
PubMed ID 11747457
Journal Biochemistry
Year 2001
Volume 40
Pages 15797-804
Authors Okishio N, Tanaka T, Nagai M, Fukuda R, Nagatomo S, Kitagawa T
Title Identification of tyrosine residues involved in ligand recognition by the phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and UV resonance Raman studies.
Related PDB
Related UniProtKB
[42]
Resource
Comments
Medline ID
PubMed ID 11478864
Journal J Mol Biol
Year 2001
Volume 311
Pages 325-40
Authors Zurdo J, Guijarro JI, Jimenez JL, Saibil HR, Dobson CM
Title Dependence on solution conditions of aggregation and amyloid formation by an SH3 domain.
Related PDB
Related UniProtKB
[43]
Resource
Comments
Medline ID
PubMed ID 11401516
Journal Biochem Biophys Res Commun
Year 2001
Volume 282
Pages 691-6
Authors Kirsch C, Wetzker R, Klinger R
Title Anionic phospholipids are involved in membrane targeting of PI 3-kinase gamma.
Related PDB
Related UniProtKB
[44]
Resource
Comments
Medline ID
PubMed ID 12367534
Journal J Mol Biol
Year 2002
Volume 322
Pages 1147-58
Authors Ventura S, Lacroix E, Serrano L
Title Insights into the origin of the tendency of the PI3-SH3 domain to form amyloid fibrils.
Related PDB
Related UniProtKB
[45]
Resource
Comments
Medline ID
PubMed ID 11986952
Journal Leukemia
Year 2002
Volume 16
Pages 894-901
Authors Jucker M, Sudel K, Horn S, Sickel M, Wegner W, Fiedler W, Feldman RA
Title Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO).
Related PDB
Related UniProtKB
[46]
Resource
Comments
Medline ID
PubMed ID 12151228
Journal Trends Biochem Sci
Year 2002
Volume 27
Pages 426-32
Authors Djordjevic S, Driscoll PC
Title Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases.
Related PDB
Related UniProtKB
[47]
Resource
Comments
Medline ID
PubMed ID 12515556
Journal Biochemistry
Year 2003
Volume 42
Pages 208-16
Authors Okishio N, Tanaka T, Fukuda R, Nagai M
Title Differential ligand recognition by the Src and phosphatidylinositol 3-kinase Src homology 3 domains: circular dichroism and ultraviolet resonance Raman studies.
Related PDB
Related UniProtKB
[48]
Resource
Comments
Medline ID
PubMed ID 12629217
Journal Proc Natl Acad Sci U S A
Year 2003
Volume 100
Pages 3275-80
Authors Fu Z, Aronoff-Spencer E, Backer JM, Gerfen GJ
Title The structure of the inter-SH2 domain of class IA phosphoinositide 3-kinase determined by site-directed spin labeling EPR and homology modeling.
Related PDB
Related UniProtKB
[49]
Resource
Comments
Medline ID
PubMed ID 15046599
Journal Biochem Soc Trans
Year 2004
Volume 32
Pages 320-5
Authors Koyasu S
Title Role of class IA phosphoinositide 3-kinase in B lymphocyte development and functions.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of a catalytic subunit and a regulatory subunit.
###
The regulatory subunit of PI3-kinase, which is composed of four domains, SH3 domain, Rho-GAP domain, and two SH2 domains. The PDB structures, 1pks, 1pkt, 1pht, 1pnj, and 2pni, correspond to the SH3 domain, whilst the PDB structure, 1pbw, correspond to the Rho-GAP domain. The rest of the structures correspond to one of the two SH2 domains. The structures, 1oo3, 1oo4, 2pna and 2pnb, correspond to the first SH2 domain, whilst the structures, 1pic, 1h9o, 1bfi, 1bfj and 1qad, correspond to the second SH2 domain.
###
Although the catalytic mechanism of this enzyme is not so clear, the reaction must proceed by single displacement mechanism.
If there is no general base, the reaction mechanism must be dissociative rather than associative (see [29]). According to the literature [29] & [46], His948 might act as a general base, which would activate the acceptor hydroxyl group. However, considering the structure of the complex with ATP, Asp950, whose mutant abolishes the activity, also may act as a general base.
Moreover, this enzyme does not have a particular Lys/Arg cluster, which stabilizes the transferred phosphate group. Possibly, Lys807 may interact with the gamma-phosphate of ATP, which would be transferred to the acceptor. Lys833 and Ser806 seem to interact with alpha-phosphate and beta-phosphate, respectively.
Instead of the basic resdiues, two magnesium ions, which should be bound to Asp836, Asn951 and Asp964, must stabilize both transferred and leaving phosphate groups (gamma- and beta-phosphate groups).
Taken together, the reaction proceeds as follows:
(1) Asp950 acts as a general base to deprotonate the acceptor group of the substrate, 3-OH.
(2) The activated acceptor group makes a nuclepophilic attack on the transferred group, the gamma-phosphate of ATP, leading to the transtion-state.
(3) Lys807 may stabilize the negative charge on the transferred group, gamma-phosphate of the transition-state, along with magnesium ions. Lys833 and Ser806 seem to stabilize the leaving groups, alpha- and beta-phosphate groups, respectively. The beta-phosphate is also stabilized by the magnesium ions.
(4) Finally, the transferred group is attached to the acceptor group, with release of ADP.

Created Updated
2004-03-18 2009-02-26