PDBsum entry 2b3r

Transferase

PDB id: 2b3r

Contents

Protein chains

124 a.a. *

Ligands

SO4 ×6

Waters ×228

* Residue conservation analysis

PDB id:

2b3r

Name:

Transferase

Title:

Crystal structure of the c2 domain of class ii phosphatidylinositide 3-kinase c2

Structure:

Phosphatidylinositol-4-phosphate 3-kinase c2 domain- containing alpha polypeptide. Chain: a, b. Synonym: phosphoinositide 3-kinase-c2-alpha, ptdins-3-kinase c2 alpha, pi3k-c2alpha, cpk-m, p170. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: pik3c2a, cpk. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.30Å R-factor: 0.197 R-free: 0.232

Authors:

L.Liu,X.Song,D.He,C.Komma,A.Kita,J.V.Verbasius,H.Bellamy,K.Miki, M.P.Czech,G.W.Zhou

Key ref:

L.Liu et al. (2006). Crystal Structure of the C2 Domain of Class II Phosphatidylinositide 3-Kinase C2{alpha}. J Biol Chem, 281, 4254-4260. PubMed id: 16338929 DOI: 10.1074/jbc.M510791200

Date:

20-Sep-05 Release date: 13-Dec-05

Protein chains

Q61194  (P3C2A_MOUSE) -  Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha from Mus musculus

Seq: 1686 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.2.7.1.137 - phosphatidylinositol 3-kinase.
• Pathway: 1-Phosphatidyl-myo-inositol Metabolism
• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl- sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H⁺
• Enzyme class 3: E.C.2.7.1.153 - phosphatidylinositol-4,5-bisphosphate 3-kinase.

Pathway:

• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- trisphosphate) + ADP + H⁺
• Enzyme class 4: E.C.2.7.1.154 - phosphatidylinositol-4-phosphate 3-kinase.

Pathway:

• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M510791200

J Biol Chem 281:4254-4260 (2006)

PubMed id: 16338929

Crystal Structure of the C2 Domain of Class II Phosphatidylinositide 3-Kinase C2{alpha}.

L.Liu, X.Song, D.He, C.Komma, A.Kita, J.V.Virbasius, G.Huang, H.D.Bellamy, K.Miki, M.P.Czech, G.W.Zhou.

ABSTRACT

Phosphatidylinositide (PtdIns) 3-kinase catalyzes the addition of a phosphate group to the 3'-position of phosphatidyl inositol. Accumulated evidence shows that PtdIns 3-kinase can provide a critical signal for cell proliferation, cell survival, membrane trafficking, glucose transport, and membrane ruffling. Mammalian PtdIns 3-kinases are divided into three classes based on structure and substrate specificity. A unique characteristic of class II PtdIns 3-kinases is the presence of both a phox homolog domain and a C2 domain at the C terminus. The biological function of the C2 domain of the class II PtdIns 3-kinases remains to be determined. We have determined the crystal structure of the mCPK-C2 domain, which is the first three-dimensional structural model of a C2 domain of class II PtdIns 3-kinases. Structural studies reveal that the mCPK-C2 domain has a typical anti-parallel beta-sandwich fold. Scrutiny of the surface of this C2 domain has identified three small, shallow sulfate-binding sites. On the basis of the structural features of these sulfate-binding sites, we have studied the lipid binding properties of the mCPK-C2 domain by site-directed mutagenesis. Our results show that this C2 domain binds specifically to PtdIns(3,4)P(2) and PtdIns(4,5)P(2) and that three lysine residues at SBS I site, Lys-1420, Lys-1432, and Lys-1434, are responsible for the phospholipid binding affinity.

Selected figure(s)

Figure 2.
Sulfate-binding sites of the mCPK-C2 domain. The 2 F[o] - F[c] maps contoured at the 1σ level are shown in purple for SBS I (A), SBS II (B), and SBS III (C), respectively. The sulfate groups are shown in bond representation, with oxygen atoms colored in red and sulfate atoms colored yellow. The surrounding water molecules are shown as green spheres. Other residues in the mCPK-C2 domain are depicted as bonds. Residues bound with sulfate ions are labeled, and the interactions are shown as dashed lines. D and E, the electrostatic potential surfaces of the mCPK-C2 domain with the bound sulfate ions are shown. Negatively charged regions are shown in red and positively charged regions in blue. The sulfate ions shown in CPK model with the same color coding as in panel A are labeled with the corresponding sulfate-binding sites. SBSs I and III (D) and SBSs I and II (E) are shown. CONSCRIPT (38) and GRASP (39) were used to generate panels A-C and panels D and E, respectively.

Figure 4.
Comparison of the mCPK-C2 domain with other type-I folded C2 domains. A, the Cα atoms of the mCPK-C2 domain in the β-sandwich core region are superposed with the Cα atoms of other type-I folded C2 domains and the C2 domains of Synaptagmin I (1RSY), Synaptagmin III (1DQV), PKCα (1DSY), and PKCβ (1A25) Their Cα chains are shown in red, purple, green, blue, and cyan, respectively. Their bound ligands and/or ions are shown in the same color as the Cα chains. For the structure of the mCPK-C2 domain, every tenth residue and each β-strand are labeled. In addition, the backbone of mCPK-C2 domain is rendered as thick sticks, and the three bound sulfate ions are rendered as ball-and-stick models with the same color coding as in Fig. 1A. B-D, comparison of the SBS I site in the mCPK-C2 domain (B) with the corresponding ligand-binding site in the PCKβ-C2 domain (C) and the PCKα-C2 domain (D). The backbones are shown in the same color as in panel A. The side chains of the residues involved in ligand binding and the bound ligand in the complex structure (sulfate, PS, and phosphate molecule in panels B, C, and D, respectively) are shown with a ball-and-stick model, in which red, blue, gray, and yellow represent the oxygen, nitrogen, carbon, and sulfur/phosphorus atoms, respectively. The bonds are colored in green for the protein and orange for the bound ligands.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 4254-4260) copyright 2006.

Figures were selected by an automated process.